CN101684471A - Biological synthesis gene cluster of nocathiacins - Google Patents

Abstract

The invention relates to a biological synthesis gene cluster of nocathiacins, in particular to cloning, sequencing, analysis, functional research and use of a biological synthesis gene cluster of an antibiotics which is nocathiacins that is produced by nocardia and has good antibacterial activity,. The whole gene cluster comprises 37 genes among which 8 genes are related to the synthesis of largering skeleton organisms, 4 genes are related to the synthesis of side chains of indoxylic acid, 6 genes are related to the synthesis of glycosyl, 5 genes are P450 oxidation reduction post-modificationenzyme genes, 2 genes are methyl transferase genes, 2 genes are resistant genes, 3 genes are adjusting genes, 3 genes are genes with unknown functions and 4 genes are related to transcription and translation. By the heterogenous expression of the biological synthesis genes, a series of novel sulfur peptide antibiotics can be generated. The genes and the proteins thereof, which are provided by theinvention, can be used for searching and discovering compounds or genes and proteins used in medicines, industry or agriculture.

Description

The biological synthesis gene cluster of promise card thiazole rhzomorph

Technical field

The invention belongs to microbial gene resource and genetically engineered field, be specifically related to the clone of the biological synthesis gene cluster of sulphur peptide antibiotics promise card thiazole rhzomorph (Nocathiacins), sequential analysis, gene functional research and application thereof.

Technical background

Promise card thiazole rhzomorph (Nocathiacins) is that a class is rich in elementary sulfur, the cyclic peptide microbiotic that amino-acid residue is highly modified, they are as crucial member in the sulphur peptide family, be at streptococcus aureus (the Methicillin-Resistant Staphylococcus aureus of screening at first to the new penicillium resistance is arranged, MRSA) and multiple chemical sproof enterococcus faecalis (Multi-Drug Resistant Enterococcus faecium arranged, MREF) growth has in the inhibiting antibiotic process, [the J.Antibiot.1998 that from pedotheque, finds, 51,715].1998, the Tokushima research centre takes the lead in from amycolatosis (Amycolatopsis sp.MJ347-81F4) separation and purification to MJ347-81F4-A (Nocathiacin I) and B, and finished their fermentation, active testing and structure determination, but do not determine its absolute configuration.2003, the Bristol-MyersSquibb institute of materia medica has found Nocathiacin I, II, III again from Nocardia bacteria (Nocardia sp.WW-12651), and it fermentation, separation and purification and active testing have been carried out, also utilize methods such as NMR, X-ray to determine its absolute configuration [J.Antibiot..2003 first, 56,226,232; Clough, B.; J.Org.Chem.2002,67,8699].

Promise card thiazole rhzomorph is the same with sulphur peptide family other microbiotic, and also to have one be core with trisubstituted pyridine, by a plurality of thiazoles and the dehydration cyclic peptide center that amino acid constituted.Wherein Nocathiacin I is structurally extremely similar to another member sugar sulphur hexides α of this family, and difference has been many one 2, and the side chain of 3-dehydrogenation alanimamides, the indolic acid unit ester bond partly that links to each other with big ring has substituted original thioester bond.

Studies show that promise card thiazole rhzomorph can suppress the growth of gram-positive microorganism well, particularly has extremely strong lethal effect to multiple chemical sproof conditioned pathogen.Wherein Nocathiacin I is 0.003 μ g/mL to the MIC value of MRSA, to streptococcus pneumoniae (the penicillin-resistantStreptococcus pneumoniae that penicillin resistance is arranged, PRSP) MIC value reaches 0.001 μ g/mL, exceeds 10-20 doubly than vancomycin.Simultaneously, it also (vancomycin-resistant Enterococci faeccium VREF) has good resistance, and the MIC value is 0.015 μ g/mL to the enterococcus faecalis that vancomycin (Vancomycin) resistance is arranged of recent appearance.And compare with vancomycin, promise card thiazole rhzomorph has significant more curative effect, the PD of Nocathiacin I, II, III to the mouse that infects MRSA ₅₀Value is respectively 0.8,0.62,0.89mg/kg, and vancomycin only is 1.3mg/kg under similarity condition.Nocathiacin I and II are as two best compounds of sulphur peptide family anti-microbial activity, also having better water-solubility than other members under low pH, may be because contain the cause [Med.Chem.Lett.2004.14.171-175] of a dimethylamino hexose in the molecule.

Find that in the recent period antibiotic mechanism of action of this class and thiostrepton are similar, also be to combine with the 23SrRNA-L11 albumen composition of 50S subunit, by stoping or promote the variation of L11 conformation, influence the identification of aa-tRNAEf-TuGTP mixture and the GTPase activity of elongation factor, thereby [the J.Am.Chem.Soc.2008 that brings into play active function that synthesizes that suppresses the bacterial body internal protein, 130,12102-12110].Its concrete structure activity relationship also is not very clear at present, but their similar cyclic peptide centers may be that it has superior active key structure by inference.

Promise card thiazole rhzomorph has just caused the great interest of scientists as the lead compound of anti-infectives of new generation from finding certainly.Consider that their solubleness does not reach the requirement of intravenous injection medicament as yet, many chemists have carried out chemical semi-synthetic transformation to it.Their bioavailability improves by added some polarity water soluble groups on Nocathiacin I in Bristol-Myers Squibb institute of materia medica: as at alkoxide [Bioorganic on the hydroxyl of pyridine ring or on the nitrogen of indolic acid side chain; Medicinal ChemistryLetters.2004,14,3743-3746]; 2, add ammonia or mercaptan [Tetrahedron Letters.2004,5,1059-1063] by the Michael addition on the 3-dehydrogenation alanimamides side chain; Perhaps remove 2 with chemical method or enzyme process, 3-dehydrogenation alanimamides obtains Nocathiacin IV, further again alkoxide or interpolation alkylamine [J.Org.Chem.2002,67,8789].But these methods often are difficult in and improve the water miscible primary formation good antibacterial activity that keeps simultaneously.And the antibiotic chemical structure of this class is extremely complicated, two people synthetic [Tetrahedron Lett.1984,25,2127 of only having finished part of module and acidic hydrolysis product during the last ten years; J.Org.Chem.1996,61,4623; J.Org.Lett.2003,5,4421; Tetrahedron Lett.1991,32,4263; AngewandteChemie.2005,117,3802-3806; Chem.Commun.2008,591-593].Finished up to the talents such as organic synthesis great master Moody and Nicolaou in recent years and to have started the complete synthesis of thiophene star A, shallow lake sulfomycin D, thiostrepton, SIM-A, GE2270A/T, complete synthesis also nobody report [Angew.Chem.Int.Ed.2007 of promise card thiazole rhzomorph, 46,7930-7954].And because the polynuclear plane of such microbiotic complexity, numerous chiral centres makes that to utilize complete synthesis method to carry out adaptation step merely various, and real cost of production is too high.

And in recent years along with the further investigation of genomics and proteomics and the fast development of new bio technology, make us utilize microorganism as " cell factory ", synthesizing natural product and analogue thereof with good biological activity and novel mechanism of action in a large number by Genetic Control becomes possibility.This also provides a new thinking for we obtain needed novel sulphur peptide antibiotics in microbe.

Therefore we are target molecule with microbe-derived promise card thiazole rhzomorph, biological synthesis gene cluster from clone's promise card thiazole rhzomorph, the method that adopts microbiology, molecular biology, biological chemistry and organic chemistry to combine is studied its biosynthesizing, illustrate its biosynthetic pathway and regulation mechanism, use the principle of metabolic engineering on this basis, the biosynthetic pathway of rational modification promise card thiazole rhzomorph, explore bioavailability better, and can pass through the mass-produced newtype drug of microbial fermentation.

Summary of the invention

The present invention relates to clone, order-checking, analysis, functional study and the application thereof of a class by the biological synthesis gene cluster of the good antibiotic active microbiotic of having of Nocardia bacteria generation-Nuo Ka thiazole rhzomorph (Nocathiacins).

Whole gene cluster comprises the nucleotide sequence or the complementary sequence (sequence 1) of 37 genes altogether among the present invention, 8 gene noc28 is wherein arranged, noc20, noc 21, and noc 22, and noc 23, noc9, noc24 and noc30 are responsible for the biosynthesizing of the big ring skeleton of Nocathiacin I; 4 gene noc25, noc26, noc 27 and noc29 are responsible for the biosynthesizing of indolic acid side chain; 6 gene noc6, noc10, noc11, noc12, noc13 and noc14 are responsible for 4-N, N-dimethyl-2,4, the biosynthesizing of 6-deoxyhexamethylose; 5 Cytochrome P450 oxidoreductase gene noc7, noc15, noc16, noc18, noc19 modifies after the redox of responsible Nocathiacin I; 2 methyl transferase gene noc8, noc36, methylate back modification and the resistance of self of responsible Nocathiacin I respectively; 2 resistant gene noc17, noc37; 3 regulatory gene noc5, noc33, noc34; 4 gene noc1s relevant with transcription and translation, noc2, noc3, noc4; And the gene noc31 of 3 unknown function, noc32, noc35.

The present invention also provides the nucleotide sequence of a coding promise card thiazole rhzomorph precursor peptide, is made up of the aminoacid sequence in the sequence 2, and called after noc28, the nucleotide sequence of its gene are arranged in sequence 1 38432-38581 base place.

The present invention also provides the nucleotide sequence of the cyclase of coding promise card thiazole rhzomorph thiazole ring formation, is made up of the aminoacid sequence in the sequence 3, and called after noc23, the nucleotide sequence of its gene are arranged in sequence 1 30980-32875 base place.

The present invention also provides the nucleotide sequence of the nadh dehydrogenase of coding promise card thiazole rhzomorph thiazole ring formation, is made up of the aminoacid sequence in the sequence 4, and called after noc22, the nucleotide sequence of its gene are arranged in sequence 1 29544-30767 base place.

The present invention also provides the nucleotide sequence of the dehydratase of the big ring skeleton formation of a coding promise card thiazole rhzomorph, is made up of the aminoacid sequence in the sequence 5, and called after noc21, the nucleotide sequence of its gene are arranged in sequence 1 26965-29523 base place.

The present invention also provides the nucleotide sequence of the dehydratase of the big ring skeleton formation of a coding promise card thiazole rhzomorph, is made up of the aminoacid sequence in the sequence 6, and called after noc20, the nucleotide sequence of its gene are arranged in sequence 1 25968-26960 base place.

The present invention also provides the nucleotide sequence of a coding free radical SAM thiamines synthetic enzyme, is made up of the aminoacid sequence in the sequence 7, and called after noc27, the nucleotide sequence of its gene are arranged in sequence 1 36848-37948 base place.

The present invention also provides the nucleotide sequence of a coding acyl group-CoA synthetic enzyme, is made up of the aminoacid sequence in the sequence 8, and called after noc25, the nucleotide sequence of its gene are arranged in sequence 1 34680-35912 base place.

The present invention also provides the nucleotide sequence of a coding acyltransferase, is made up of the aminoacid sequence in the sequence 9, and called after noc26, the nucleotide sequence of its gene are arranged in sequence 1 35933-36820 base place.

The present invention also provides the oxydase of coding SAM dependence or the nucleotide sequence of methyltransgerase, is made up of the aminoacid sequence in the sequence 10, and called after noc29, the nucleotide sequence of its gene are arranged in sequence 1 38714-39976 base place.

The present invention also provides the nucleotide sequence of the two methyltransgerases of coding N-, is made up of the aminoacid sequence in the sequence 11, and called after noc10, the nucleotide sequence of its gene are arranged in sequence 1 14990-15703 base place.

The present invention also provides the nucleotide sequence of the methyltransgerase on 3 C of a coding NDP-hexose, is made up of the aminoacid sequence in the sequence 12, and called after noc11, the nucleotide sequence of its gene are arranged in sequence 1 15728-16972 base place.

The present invention also provides the nucleotide sequence of a coding NDP-hexose-3-ketoreductase, is made up of the aminoacid sequence in the sequence 13, and called after noc12, the nucleotide sequence of its gene are arranged in sequence 1 16984-17970 base place.

The present invention also provides a coding dTDP-4-ketone-6-deoxyglucose 2, and the nucleotide sequence of 3-dehydratase is made up of the aminoacid sequence in the sequence 14, and called after noc13, the nucleotide sequence of its gene are arranged in sequence 1 17988-19418 base place.

The present invention also provides the nucleotide sequence of the transaminase on 4 C of a coding NDP-6-DDG, form by the aminoacid sequence in the sequence 15, called after noc14, the nucleotide sequence of its gene are arranged in sequence 1 19424-20560 base place.

The present invention also provides the nucleotide sequence of the transaminase of an encoding glycosyl transferring enzyme, is made up of the aminoacid sequence in the sequence 16, and called after noc6, the nucleotide sequence of its gene are arranged in sequence 1 11505-12683 base place.

The present invention also provides the nucleotide sequence of a Codocyte cytochrome p 450 oxydo-reductase, is made up of the aminoacid sequence in the sequence 17, and called after noc7, the nucleotide sequence of its gene are arranged in sequence 1 12704-13912 base place.

The present invention also provides the nucleotide sequence of a Codocyte cytochrome p 450 oxydo-reductase, is made up of the aminoacid sequence in the sequence 18, and called after noc15, the nucleotide sequence of its gene are arranged in sequence 1 20591-21703 base place.

The present invention also provides the nucleotide sequence of a Codocyte cytochrome p 450 oxydo-reductase, is made up of the aminoacid sequence in the sequence 19, and called after noc16, the nucleotide sequence of its gene are arranged in sequence 1 21696-22934 base place.

The present invention also provides the nucleotide sequence of a Codocyte cytochrome p 450 oxydo-reductase, is made up of the aminoacid sequence in the sequence 20, and called after noc18, the nucleotide sequence of its gene are arranged in sequence 1 23507-24649 base place.

The present invention also provides the nucleotide sequence of a Codocyte cytochrome p 450 oxydo-reductase, is made up of the aminoacid sequence in the sequence 21, and called after noc19, the nucleotide sequence of its gene are arranged in sequence 1 24646-25947 base place.

The present invention also provides the nucleotide sequence of a coding methyltransgerase, is made up of the aminoacid sequence in the sequence 22, and called after noc8, the nucleotide sequence of its gene are arranged in sequence 1 13909-14532 base place.

The present invention also provides the nucleotide sequence of a coding methyltransgerase, is made up of the aminoacid sequence in the sequence 23, and called after noc36, the nucleotide sequence of its gene are arranged in sequence 1 43983-44768 base place.

The present invention also provides the nucleotide sequence of a coding bleomycin resistance protein, is made up of the aminoacid sequence in the sequence 24, and called after noc17, the nucleotide sequence of its gene are arranged in sequence 1 22956-23480 base place.

The present invention also provides the nucleotide sequence of a coding phosphor hydrochlorate ABC transporter, is made up of the aminoacid sequence in the sequence 25, and called after noc37, the nucleotide sequence of its gene are arranged in sequence 1 44914-45423 base place.

The present invention also provides the nucleotide sequence of the transcription regulatory protein of a coding SARP family, is made up of the aminoacid sequence in the sequence 26, and called after noc5, the nucleotide sequence of its gene are arranged in sequence 1 10404-11387 base place.

The present invention also provides the nucleotide sequence of a coding heat shock protein(HSP), is made up of the aminoacid sequence in the sequence 27, and called after noc33, the nucleotide sequence of its gene are arranged in sequence 1 42031-42456 base place.

The present invention also provides the nucleotide sequence of a coding hsp18 transcription regulaton factor, is made up of the aminoacid sequence in the sequence 28, and called after noc34, the nucleotide sequence of its gene are arranged in sequence 1 42565-43173 base place.

The present invention also provides the nucleotide sequence of the signal factor of a coding RNA polysaccharase ECF-subtribe, is made up of the aminoacid sequence in the sequence 29, and called after noc3, the nucleotide sequence of its gene are arranged in sequence 1 8731-9867 base place.

The present invention also provides the nucleotide sequence of the signal factor of a coding ATP enzyme, is made up of the aminoacid sequence in the sequence 30, and called after noc4, the nucleotide sequence of its gene are arranged in sequence 1 9968-10387 base place.

The present invention also provides the nucleotide sequence of an encoding D GPFAETKE family protein, is made up of the aminoacid sequence in the sequence 31, and called after noc2, the nucleotide sequence of its gene are arranged in sequence 1 8282-8725 base place.

The present invention also provides the nucleotide sequence of a coding 50S ribosomal protein L 18, is made up of the aminoacid sequence in the sequence 32, and called after noc1, the nucleotide sequence of its gene are arranged in sequence 1 7731-8084 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 33, and called after noc9, the nucleotide sequence of its gene are arranged in sequence 1 14529-14984 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 34, and called after noc24, the nucleotide sequence of its gene are arranged in sequence 1 32902-34683 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 35, and called after noc30, the nucleotide sequence of its gene are arranged in sequence 1 40174-40914 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 36, and called after noc31, the nucleotide sequence of its gene are arranged in sequence 1 41001-41408 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 37, and called after noc32, the nucleotide sequence of its gene are arranged in sequence 1 41492-41953 base place.

The present invention also provides a proteic nucleotide sequence of coding unknown function, is made up of the aminoacid sequence in the sequence 38, and called after noc35, the nucleotide sequence of its gene are arranged in sequence 1 43228-43758 base place.

The complementary sequence of sequence 1 can obtain according to DNA base complementrity principle.The nucleotide sequence of sequence 1 or partial nucleotide sequence can be by polymerase chain reaction (PCR) or with suitable digestion with restriction enzyme corresponding D NA fragment or utilize other suitable technique to obtain.The present invention also provides the approach that obtains to comprise at least the recombinant plasmid of dna fragmentation in the partial sequence 1.

The present invention also provides promise card thiazole rhzomorph biosynthetic microbe approach, and the gene of one of them includes the nucleotide sequence in the sequence 1 at least.

Nucleotide sequence provided by the present invention or partial nucleotide sequence, the DNA that can utilize the method for polymerase chain reaction (PCR) or comprise sequence of the present invention obtains from the other biological body and the similar gene of promise card thiazole rhzomorph biosynthesis gene with methods such as Southern hybridization as probe.

Comprise nucleotide sequence provided by the present invention or at least the cloned DNA of partial nucleotide sequence can be used for from Nocardia bacteria Nocardia sp.WW-12651 genomic library more library, location plasmid.These library plasmids comprise the partial sequence among the present invention at least, also include the DNA that former adjacent domain is not cloned in the Nocardia sp.WW-12651 genome.

Nucleotide sequence provided by the present invention or at least partial nucleotide sequence can be modified or be suddenlyd change.These approach comprise insertion, displacement or disappearance, the polymerase chain reaction, mistake mediation polymerase chain reaction, the locus specificity sudden change, not homotactic reconnecting, the different piece of sequence or carry out orthogenesis (DNA shuffling) with the homologous sequence in other sources, or by ultraviolet ray or chemical reagent mutagenesis etc.

Comprise nucleotide sequence provided by the present invention or at least the clone gene of partial nucleotide sequence can in foreign host, express to obtain the meta-bolites of corresponding enzyme or other higher biological activitys or output by suitable expression system.These foreign host comprise streptomycete, pseudomonas, intestinal bacteria, genus bacillus, yeast, plant and animal etc.

Aminoacid sequence provided by the present invention can be used for separating needed albumen and can be used for the preparation of antibody.

Comprise aminoacid sequence provided by the present invention or at least the polypeptide of partial sequence may after remove or substituting some amino acid, still have biological activity even new biologic activity is arranged, perhaps improved output or optimized the albumen dynamic characteristic or other character of being devoted to obtain.

Comprise nucleotide sequence provided by the present invention or at least partial nucleotide sequence gene or gene cluster can be expressed in heterologous host and understand their functions in host's metabolic chain by the DNA chip technology.

Comprise nucleotide sequence provided by the present invention or at least the gene or the gene cluster of partial nucleotide sequence can come construction recombination plasmid to obtain its biosynthetic pathway by genetic recombination, also can and then obtain new biosynthetic pathway by insertion, displacement, disappearance or inactivation.

Comprise nucleotide sequence provided by the present invention or the clone gene of partial nucleotide sequence or dna fragmentation can obtain new promise card thiazole rhzomorph analog by interrupting biosynthetic one or several step of promise card thiazole rhzomorph at least.Comprise the output that dna fragmentation or gene can be used for improving promise card thiazole rhzomorph or derivatives thereof, the invention provides the approach that in genetically engineered microorganism, improves output.

The biosynthetic precursor peptide of nucleotide sequence coded rrna mechanism promise card thiazole rhzomorph provided by the present invention can be by inserting, replace or disappearance, the polymerase chain reaction, mistake mediation polymerase chain reaction, the locus specificity sudden change, not homotactic reconnecting, the different piece of sequence or carry out orthogenesis (DNA shuffling) with the homologous sequence in other sources, methods such as ultraviolet ray or chemical reagent mutagenesis produce new sulphur peptide antibiotics or other polypeptide class meta-bolitess.

Structural units such as comprising nucleotide sequence coded albumen provided by the present invention can catalysis synthetizing thiazolium ring, hydroxylation pyridine ring, indolic acid, and can be by recombinating with the biosynthetic pathway or the part biological route of synthesis of other natural products, obtaining to comprise has these structural units and has better bioactive meta-bolites.

Comprise big ring skeleton and its analog that nucleotide sequence coded albumen provided by the present invention can the synthetic promise card thiazole rhzomorph of catalysis.

Comprise nucleotide sequence coded albumen provided by the present invention and can catalysis synthesize 4-N, N-dimethyl-2,4, the 6-deoxyhexamethylose, and can obtain new glycation product by recombinating with the biosynthetic pathway or the part biological route of synthesis of other natural products.

The back modifying factor of promise card thiazole rhzomorph provided by the present invention provides the approach that obtains analogue by genetic modification, and the redox reaction that is comprised also can have other application.

In a word, all relevant genes of promise card thiazole rhzomorph biosynthesizing and the albumen information of comprising provided by the present invention can help people to understand the biosynthesizing mechanism of sulphur peptide antibiotics, for further genetic modification provides material and knowledge.Gene provided by the present invention and protein thereof also can be used for seeking and find can be used for medicine, industry or agriculture compound or gene, albumen.

Description of drawings

Fig. 1: the chemical structure of promise card thiazole rhzomorph.

Fig. 2: the gene structure and the restriction mapping of promise card thiazole rhzomorph biological synthesis gene cluster.(A) the glutinous grain of 6 overlappings has been represented the DNA zone of Nocardia bacteria Nocardia sp.WW-12651 genome 45kb, and S represents Restriction enzyme Sma I, and entity is represented by the part of dna sequencing, the probe portion of the thick vertical line expressive notation of black; (B) genomic constitution of promise card thiazole rhzomorph biological synthesis gene cluster.

Fig. 3: the biosynthetic pathway of the big ring skeleton of promise card thiazole rhzomorph of proposition.

Fig. 4: the biosynthetic pathway of the promise card thiazole rhzomorph indolic acid side chain of proposition.

Fig. 5: the promise card thiazole rhzomorph 4-N of proposition, N-dimethyl-2,4, the biosynthetic pathway of 6-deoxyhexamethylose.

Fig. 6: high performance liquid chromatography-mass spectrum (HPLC-MS) of Nocardia sp.WW-12651 wild-type tunning Nocathiacin I is analyzed.

(A) high performance liquid chromatography; (B) mass spectrum

Fig. 7: the portion gene relevant with the biosynthesizing of the big ring skeleton of promise card thiazole rhzomorph is to the allos complementation of similar gene in the nosiheptide gene cluster with frame deletion mutantion strain.

(A) nosiheptide produces the HPLC-MS detection of bacterium Streptomyces actuosus ATCC25421 wild-type tunning

(B) nosiheptide nosE detects with the HPLC-MS of frame deletion mutantion strain tunning

(C) HPLC-MS of promise card thiazole rhzomorph noc21 allos covering mutant strain tunning detects

(D) nosiheptide nosD detects with the HPLC-MS of frame deletion mutantion strain tunning

(E) HPLC-MS of promise card thiazole rhzomorph noc20 allos covering mutant strain tunning detects

Fig. 8: the portion gene relevant with the biosynthesizing of promise card thiazole rhzomorph indolic acid side chain is to the allos complementation of similar gene in the nosiheptide gene cluster with frame deletion mutantion strain.

(A) nosiheptide produces the HPLC-MS detection of bacterium Streptomyces actuosus ATCC25421 wild-type tunning

(B) nosiheptide nosI detects with the HPLC-MS of frame deletion mutantion strain tunning

(C) HPLC-MS of promise card thiazole rhzomorph noc25 allos covering mutant strain tunning detects

(D) nosiheptide nosL detects with the HPLC-MS of frame deletion mutantion strain tunning

(E) HPLC-MS of promise card thiazole rhzomorph noc27 allos covering mutant strain tunning detects

Fig. 9: in the promise card thiazole rhzomorph biological synthesis gene cluster after the part P450 redox modifying factor to the allos complementation of similar gene in the nosiheptide gene cluster with frame deletion mutantion strain.

(A) nosiheptide produces the HPLC-MS detection of bacterium Streptomyces actuosus ATCC25421 wild-type tunning

(B) nosiheptide nosC detects with the HPLC-MS of frame deletion mutantion strain tunning

(C) HPLC-MS of promise card thiazole rhzomorph noc19 allos covering mutant strain tunning detects

(D) nosiheptide nosB detects with the HPLC-MS of frame deletion mutantion strain tunning

(E) HPLC-MS of promise card thiazole rhzomorph noc7 allos covering mutant strain tunning detects

Figure 10: the heterogenous expression of modifying factor in nosiheptide generation bacterium Streptomyces actuosus ATCC25421 after the part P450 redox in the promise card thiazole rhzomorph biological synthesis gene cluster.

(A) nosiheptide produces the HPLC-MS detection of bacterium Streptomyces actuosus ATCC25421 wild-type tunning

(B) HPLC-MS of promise card thiazole rhzomorph noc16 heterogenous expression mutant strain tunning detects

(C) HPLC-MS of promise card thiazole rhzomorph noc18 heterogenous expression mutant strain tunning detects

The chemical structure of nosiheptide analog A

The chemical structure of nosiheptide analog B.

Nomenclature

Fig. 1 Nocathiacin I: promise card thiazole rhzomorph I; Nocathiacin II: promise card thiazole rhzomorph II; NocathiacinIII: promise card thiazole rhzomorph III; MJ347-81F4-B: the demethylation product of promise card thiazole rhzomorph I.

Fig. 2 (A) B ₃: glutinous grain pDY2-61-B ₃, D ₂: glutinous grain pDY2-61-D ₂, C ₂: glutinous grain pDY2-61-C ₂, A ₁: glutinous grain pDY2-61-A ₁, C ₄: glutinous grain pDY2-61-C ₄Letter S represents the SmaI restriction enzyme site;

(B) suger 4-N, N-dimethyl-2,4, modifying factor Indole acid promise card thiazole rhzomorph indolic acid side chain biosynthesis gene resistance resistant gene regulation regulatory gene Unknown unknown gene after the big ring skeleton of the 6-deoxyhexamethylose biosynthesis gene cyclopeptide promise card thiazole rhzomorph biosynthesis gene oxidation promise card thiazole rhzomorph P450 redox.

Gene noc20,21,22 in the promise card thiazole rhzomorph gene cluster of describing in corresponding respectively this specification sheets of Fig. 3 Noc20,21,22,23,23 coded albumen, LP represents the signal peptide of promise card thiazole rhzomorph.

Gene noc25,26,27 in the promise card thiazole rhzomorph gene cluster of describing in corresponding respectively this specification sheets of Fig. 4 Noc25,26,27,29,29 coded albumen, Ado represents free radical.

Gene noc6,10,12,13 in the promise card thiazole rhzomorph gene cluster of describing in corresponding respectively this specification sheets of Fig. 5 Noc6,10,12,13,14,14 coded albumen.

Fig. 6 (A) 15min is that retention time (B) 1437 of Nocathiacin I is the molecular ion peak of Nocathiacin I.

Embodiment:

The present invention is described in more detail below in conjunction with Fig. 1-Fig. 6.

1. N in the promise card thiazole rhzomorph biological synthesis gene cluster, the clone of N-dimethyl enzyme gene fragment:

Although the research of relevant sulphur peptide antibiotics biosynthesizing aspect just began as far back as the end of the seventies in last century, all fail effectively to break through in the research of microbe intracellular metabolite approach about them up to now.Early stage investigator has mainly finished the amino acid precursor labelling experiment (C of thiostrepton (Thiostrepton), nosiheptide (Nosiheptide), sulphur peptimycin I (sulfomycin I), GE2270A, A10255G/B/E, promise card thiazole rhzomorph (Nocathiacins) etc. ¹³, C ¹⁴, H ², H ³, N ¹⁵Deng), and inferred the possible biosynthetic pathways of they part primary structures thus: as think that wherein thiazole or thiazoline ring derive from halfcystine and Serine; Indolic acid or quinaldinic acid structure are then transformed through multistep by tryptophane and obtain; Think that also the azepine six-ring of their core textures forms [J.Am.Chem.Soc.1979,101,5069 by [4+2] cycloaddition reaction; 1988,110,5800; 1993,115,7557; 1993,115,7992; 1995,117,7606; 1996,118,11363; Biorg.Med.Chem.1996,4,1135; J.Antibiot.1992,45,1499; 2001,54,1066; J.Chem.Soc.Chem.Commun.1993,1612; Acc.Chem.Res.1993,26,116; Tetrahedron Letters.2008,49,6265-6268.].

Labelling experiment shows that equally also this class microbiotic has similar amino acid precursor mostly, and this illustrates that in a sense they may be to adopt similar biosynthetic pathway to obtain in microbe.And the biosynthetic pathway of typical poly-peptides natural product can be divided into two classes substantially in the microbe: rrna approach and non-ribosomal approach.Floss group once suppresses result of experiment according to paraxin and infers that this class microbiotic may be to adopt non-ribosomal approach synthetic.Investigators have attempted a large amount of methods and have cloned the antibiotic biological synthesis gene cluster of this class subsequently, as mutant strain complementation, reverse genetics, resistant gene is that the gene fragment of probe, coding rrna approach precursor peptide is that the conserved sequence of probe, non-ribosomal approach biosynthesis gene is methods such as primer, transposon interrupt at random, but does not all have successfully.This just points out us need seek a brand-brand-new way and clones the antibiotic biological synthesis gene cluster of this class.

Be distributed in these characteristics on chromosomal the same area according to the biosynthesis gene of the glycosyl of glycopeptide antibiotics and precursor skeleton is mostly chain, the inventor determines the biosynthesis gene of deoxidation aminosugar from clone Nocathiacin I, clones the biological synthesis gene cluster of whole molecule.We are at first according to biosynthetic pathway [Antimicrobial Agents AndChemotherapy, 1999,43, the 1565-1573 of a large amount of microbe-derived natural product deoxidation glycosyls; Chemistry ﹠amp; Biology, 2004,11,959-969; Molecular Microbiology, 2000,37,752-762.] inferred 4-N among the Nocathiacin I, N-dimethyl-2,4, the biosynthetic pathway that the 6-deoxyhexamethylose is possible, and choose the N that may be present in this approach catalysis later stage, the conserved sequence of N-dimethyl transferring enzyme, PCR primer Dimeth-For1:5 '-GCTGACGTCGCCTGCGGSAC (CG) GG (ATCG) that has designed degeneracy is (ATCG) (ATCG) CA-3 and Dimeth-Rev2:5 '-CGCG AACGT (GC) TC (GC) GG (AG) AA CCACCA (ATGC) GG (ATGC) TC-3 ' (GAT), total DNA with Nocardia sp.WW-12651 is that template is carried out pcr amplification then, obtains the PCR product of about 0.3kb, is cloned into the pSP72 carrier, find and known N that through sequencing analysis N-dimethyl transferase gene has very high homology.

2. the clone of promise card thiazole rhzomorph biological synthesis gene cluster, sequential analysis and functional analysis:

With above-mentioned N of being cloned into, N-dimethyl enzyme gene fragment is labeled as probe with digoxin, and the genomic library of the Nocardia sp.WW-12651 that builds is screened, and obtains 6 altogether and inserts the glutinous grain that fragments overlap each other, and is respectively: cDY446-2-47-A ₁, B ₃, C ₂, C ₄, D ₂, D ₄, contained DNA zone (Fig. 2-A) of the about 50kb of karyomit(e).Choose the glutinous grain cDY446-2-47-B of high order end and low order end in the restriction enzyme digestion physical map ₃, C ₂Carry out the subclone order-checking, find the DNA zone of the 45.560kb of mensuration by analysis of biological information, GC content is 73.3%, (open readingframe, ORF), wherein relevant with the biosynthesizing of promise card thiazole rhzomorph has 37 to have comprised 44 open reading frames altogether.The functional analysis of each gene sees Table 1.

The functional analysis of each gene and proteins encoded in the table 1 promise card thiazole rhzomorph biological synthesis gene cluster

Gene	Amino acid number	Similar protein	Identity/similarity %	Infer function
					??orf(-7)	??445	??SSAG_06220(YP_002178248)	??72/82	The PKS synthetic enzyme
??orf(-6)	??677	??SCO6280(NP_630378)	??57/68	Regulate albumen
					??orf(-5)	??367	??ORF7(AAZ94395)	??70/80	Methoxy propyl diacid synthetic proteins
??orf(-4)	??362	??OzmD(ABA39084)	??69/77	Acyl group ACP desaturase
					??orf(-3)	??87	??HbmJ(AAY28231)	??56/74	The acyl group translocator
??orf(-2)	??222	??OzmF(ABS90468)	??66/79	The o-methyltransgerase
					??orf(-1)	??275	??ORF1(AAZ94392)	??64/77	Desaturase
??noc1	??117	??Rp1R(YP_001108909)	??44/55	50S rrna L18 albumen
					??noc2	??147	??SAV_960(NP_822135)	??92/96	The DGPFAETKE family protein
??noc3	??378	??Sig12(NP_822136)	??88/93	ECF subfamily RNA polymerase signal factor
					??noc4	??139	??AAur_1361(YP_947141)	??29/47	Agnoprotein
??noc5	??327	??TylS(AAD40804)	??52/67	The approach specificity is regulated albumen

??noc6	??392	??CalG4(AAM70365)	??42/57	Glycosyltransferase
					??noc7	??402	??PlaO5(ABB69764)	??38/50	FscP
??noc8	??207	??Adeh_3203(YP_466408)	??45/58	Methyltransgerase Class1 2
					??noc9	??151	??Francci3_4114(YP_483191)	??62/76	Agnoprotein
??noc10	??237	??C1027-ORF7(AAL06660)	??53/66	The N-methyltransgerase
					??noc11	??414	??EU443633(ACB37738)	??62/73	The methyltransgerase that glycosyl carbon is three
??noc12	??328	??gra-orf26(CAA09647)	??51/60	Three keto reductases of glycosyl
					??noc13	??476	??SnogH(CAA12009)	??56/64	DTDP-4-ketone-6-deoxyglucose 2, the 3-desaturase
??noc14	??378	??MdpA5(ABY66023)	??65/75	Transaminase
					??noc15	??370	??pSLA2-L_p037(NP_851459)	??25/41	The P450 hydroxylase
??noc16	??412	??SSDG_02678(YP_002198948)	??30/43	FscP
					??noc17	??174	??Acid345_0564(YP_589643)	??33/50	The bleomycin resistance protein
??noc18	??380	??GdnH(AAO61204)	??28/41	Cytochrome P450
					??noc19	??426	??MycG(BAA03672)	??39/55	Cytochrome P450
??noc20	??330	??BC5083(NP_834751)	??25/48	Dehydratase
					??noc21	??852	??BC5084(NP_834752)	??21/42	Dehydratase
??noc22	??479	??BC5081(NP_834749)	??25/38	Nadh oxidase
					??noc23	??631	??BC5085(NP_834753)	??31/50	Heterocyclization albumen
??noc24	??593	??BC1250(NP_831034)	??23/38	Agnoprotein
					??noc25	??410	??BlinB01000376(ZP_00381324)	??27/39	Acyl-CoA synthetase
??noc26	??295	??Magn03008449(ZP_00053841)	??30/41	Acyltransferase
					??noc27	??366	??CBB_A0178(ZP_02619422)	??38/60	The thiamines synthetic proteins
??noc28	??49	??BC_5090(AAP11959)	??39/65	Precursor peptide
					??noc29	??420	??Zbm-Orf26(ACG60749)	??33/49	The methyltransgerase that SAM relies on
??noc30	??246	??BC5082(NP_834750)	??22/39	Agnoprotein
					??noc31	??135	??DUF326(ZP_04331324)	??65/76	Agnoprotein
??noc32	??153	??SvirDRAFT_3834(ZP_04508930)	??42/53	Agnoprotein
					??noc33	??141	??hspX(NP_821634)	??66/84	Heat shock protein(HSP)
??noc34	??202	??SAV_691(NP_821866)	??50/65	The hsp18 transcription regulaton factor
					??noc35	??176	??Mjls_2670(YP_001070941)	??61/76	Agnoprotein
??noc36	??261	??Noca_3743(YP_924930)	??73/81	Methyltransgerase Class1 1
					??noc37	??169	??Mvan_5092(YP_955869)	??51/63	ABC phosphoric acid salt shifts enzyme

3. promise card thiazole rhzomorph biological synthesis gene cluster border is determined

According to the functional analysis of gene coded protein, the biological synthesis gene cluster of our preliminary judgement promise card thiazole rhzomorph be from gene noc1 to noc37, totally 37 open reading frames.Wherein 1 gene (noc28) is responsible for the precursor peptide of coding promise card thiazole rhzomorph, and 7 genes (noc 21 for noc28, noc20, and noc 22, and noc 23, noc9, noc24 and noc30) are responsible for the precursor peptide of noc28 coding is modified, and form whole big ring skeleton; It is precursor that 4 genes (noc25, noc26, noc 27 and noc29) are responsible for the tryptophane, synthesis of indole acid side chain; 6 genes (noc6, noc10, noc11, noc12, noc13 and noc14) are responsible for 4-N, N-dimethyl-2,4, the biosynthesizing of 6-deoxyhexamethylose; 5 Cytochrome P450 oxidoreductase genes (noc7, noc15, noc16, noc18 noc19) is responsible for modifying after the redox of Nocathiacin I; (noc8 noc36) is responsible for back modification of methylating of Nocathiacin I and the resistance of self respectively to 2 methyl transferase genes; Also have in addition 2 resistant genes (noc17, noc37); 3 regulatory gene (noc5, noc33, noc34); 4 genes relevant with transcription and translation (noc1, noc2, noc3, noc4); And the gene of 3 unknown function (noc31, noc32, noc35).Because orf (1)-orf (8) is and the relevant gene of methoxy propyl diacid biosynthesizing, gene noc1-noc3 then encode respectively 50S rrna L18 albumen, DGPFAETKE family protein and ECF subfamily RNA polymerase signal factor, these genes may be relevant with the method for the transcribing translation of promise card thiazole rhzomorph precursor peptide.So the right side boundary of promise card thiazole rhzomorph biological synthesis gene cluster should be between orf (1)-noc1.The gene noc31-37 on this sequence right side is some regulatory gene and resistant gene, we can't determine they and the biosynthetic dependency of promise card thiazole rhzomorph, so the left border of promise card thiazole rhzomorph biological synthesis gene cluster also is not very clear, remains further to be probed into.

4. the biosynthesizing of the big ring skeleton of promise card thiazole rhzomorph

It is relevant with the biosynthesizing of its big ring skeleton to have 8 genes in the biological synthesis gene cluster of promise card thiazole rhzomorph.Noc28 wherein, the precursor peptide of coding promise card thiazole rhzomorph, the amino acid precursor of its C end structure peptide sequence SCTTCECSCSCSS and the big ring skeleton of promise card thiazole rhzomorph fits like a glove in proper order, and the N end is rich in the signal peptide part of hydrophobic amino acid, then mainly be responsible for the identification of precursor peptide, and mediate it at intracellular transport.This has also confirmed that from gene level the big ring skeleton of promise card thiazole rhzomorph should be to come synthetic according to rrna mechanism.This process is similar to cell peptide and proteinic synthetic, at first progressively forms the poly-peptide chain precursor of promise card thiazole rhzomorph in rrna through transcription and translation.Then the hydrolysis from the rrna of this precursor discharges, again by the cyclodehydration enzyme catalysis of noc23 coding wherein the sulfydryl attack on the halfcystine face carbonyl on the Serine, forms 5 yuan of N heterocycles, then slough a part water, the formation thiazoline.A part hydrogen is sloughed in the oxydo-reductase effect that is relied on by the NADH of noc22 coding then, changes thiazoline into thiazole.Next under the catalysis of the dehydratase of noc20 or noc21 coding, slough the hydroxyl on the serine residue, form 2, the 3-dehydroalanine further forms hydroxylation dehydropiperidine six-ring by intramolecularly Diels-Alder reaction.And then under the effect of the agnoprotein of noc30 coding and a series of dehydratase and oxydo-reductase, form hydroxylation pyridine cyclic peptide center, thereby made up maximum in a promise card thiazole rhzomorph cyclic peptide structures through polystep reaction.Whole process as shown in Figure 3.

5. the biosynthesizing of skatole acid structural unit

The biosynthetic pathway of skatole acid structural unit as shown in Figure 4.At first be precursor with the tryptophane, through the proteic catalysis of radical S-adenosylmethionine (AdoMet) type of noc27 coding a series of intramolecular rearrangements take place, hydrolysis decarboxylation forms 3-skatole-2-formic acid structure again.Then activate the carboxyl of indolic acid, be converted into the CoA-thioester bond by the acyl group-CoA synthetic enzyme of noc25 coding.Then under the effect of the acyltransferase of noc26 coding, form the indolic acid side chain and be connected with thioester bond between the big ring skeleton of promise card thiazole rhzomorph.Further shift methyl on the methionine(Met) to the carbon of 4 of indolic acid by the methyltransgerase of noc29 coding, act on a last hydroxyl on 4 carbon by the oxydo-reductase in the gene cluster again, realizing under the effect of a series of relevant enzyme that the indolic acid side chain is connected with the big ester bond that encircles between skeleton at last.Wherein 4 of indolic acid methylate may occur in side chain and big ring skeleton thioester bond and is connected before or after the connection.

6.4-N, N-dimethyl-2,4, the unitary biosynthesizing of 6-deoxyhexamethylose

It is relevant with the biosynthesizing of its glycosyl to have 6 genes in the biological synthesis gene cluster of promise card thiazole rhzomorph.At first the D-glucose of a part phosphorylation is activated under the effect of dNDP-D-glucose synthetic enzyme, then by dNDP-D-glucose-4,6-dehydratase catalytic dehydration forms ketone group at 4, again by 2 of noc13 coding, the effect of 3-dehydratase is sloughed another molecular water and is formed 3,4-ketone-6-deoxyhexamethylose intermediate, then under the catalysis of the 3-ketone-reductase enzyme of noc12 coding 3 be reduced into hydroxyl, through 3, behind the effect generation epimerization of 5 isomerases, again under the effect of the methyltransgerase of noc11 coding on 3 a methyl, again by transamination enzyme catalysis amino on 4 of noc14 coding, then at the N of noc10 coding, on amino, add two methyl under the effect of N-dimethyl transferring enzyme, glycosyltransferase by the noc6 coding shifts this glycosyl to the big ring skeleton of promise card thiazole rhzomorph at last, and whole process as shown in Figure 5.

7. the back modification of promise card thiazole rhzomorph

Have 5 Cytochrome P450 oxidoreductase gene noc7 in the biological synthesis gene cluster of promise card thiazole rhzomorph, noc15, noc16, noc18, noc19, may with a series of redox in the promise card thiazole rhzomorph biosynthetic pathway after modify relevant.The respectively hydroxylation on the catalysis promise card thiazole rhzomorph pyridine ring and the hydroxylation of glutamic acid gamma position of noc7 and noc19 wherein, noc16 and noc18 be the hydroxylation on the hydroxylation on the catalyzing indole acid N and 3 methyl respectively.Also having an agnoprotein noc9 in this gene cluster, may be that the shearing of being responsible for the Serine side chain forms amide structure.

8. the application of promise card thiazole rhzomorph biological synthesis gene cluster

On the basis of clone, analysis promise card thiazole rhzomorph biological synthesis gene cluster, we have also developed the universal method of other sulphur peptide antibiotics biological synthesis gene clusters of cover quick clone.As utilizing the amino acid conserved sequence that wherein forms relevant cyclo(de)hydrase Noc23 with thiazole ring, design PCR primer has been cloned the biological synthesis gene cluster of thiostrepton, nosiheptide, siomycin etc., also utilizes the gene order relevant with the biosynthesizing of the big ring skeleton of promise card thiazole rhzomorph to clone the biological synthesis gene cluster of theiomycetin by the method for genome scanning simultaneously.

On this basis, we further analyze the similarity that has compared these gene clusters and biosynthetic pathway.As one having 15 intimate genes (table 2) in the biological synthesis gene cluster of promise card thiazole rhzomorph and nosiheptide, wherein comprised 8 with the relevant gene of big ring skeleton biosynthesizing, 4 with the synthetic relevant gene of indolic acid side chain, 2 P450 oxidoreductase genes and 1 regulatory gene, and these genes put in order also similar substantially with transcriptional orientation.We at first by in the system that produces bacterium at nosiheptide to the same frame disappearance tentative confirmation of the similar gene of partial function these genes and the biosynthetic dependency of nosiheptide, we import to these with carrying out the allos complementation in the frame deletion mutantion strain with the similar gene in the promise card thiazole rhzomorph gene cluster again on this basis, detect through fermentation and LC-MS, recovery has produced nosiheptide, has further confirmed these similar genes and big ring skeleton and indolic acid side chain synthetic dependency.Simultaneously we also produce heterogenous expression in the thalline system by 2 P450 oxidoreductase gene noc16 and noc18 at nosiheptide, tentative confirmation they possible functions.

The homology of functional similarity gene relatively in table 2 promise card thiazole rhzomorph and the nosiheptide biological synthesis gene cluster

??Nos	??Noc	??Identities	??Positives
				??NosD	??Noc20	??183/328(55％)	??215/328(65％)
??NosE	??Noc21	??506/885(57％)	??586/885(66％)
				??NosF	??Noc22	??222/474(46％)	??253/474(53％)
??NosG	??Noc23	??411/642(64％)	??459/642(71％)

??NosH	??Noc24	??304/608(50％)	??354/608(58％)
				??NosI	??Noc25	??55/91(60％)	??64/91(70％)
??NosJ	??Noc26	??120/229(52％)	??151/229(65％)
				??NosL	??Noc27	??280/357(78％)	??315/357(88％)
??NosM	??Noc28	??41/48(85％)	??45/48(93％)
				??NosN	??Noc29	??296/391(75％)	??336/391(85％)
??NosO	??Noc30	??108/261(41％)	??145/261(55％)
				??NosP	??Noc5	??144/266(54％)	??187/266(70％)
??NosC	??Noc19	??289/406(71％)	??336/406(82％)
				??NosA	??Noc9	??88/136(64％)	??107/136(78％)
??NosB	??Noc7	??221/450(49％)	??266/450(59％)

Embodiment below further is provided, and these embodiments help to understand the present invention, only do not limit range of application of the present invention with explaining.

Embodiment 1

Promise card thiazole rhzomorph produces the extraction of the total DNA of bacterium Nocardia bacteria Nocardia sp.WW-12651:

With 100 μ L Nocardia sp.WW-12651 mycelia suspension inoculations in 3mL TSB liquid nutrient medium, 30 ℃, 250rpm, the about 36hr of shaking culture reaches the logarithmic phase later stage.Getting 3mL is inoculated among the 50mL TSB and (contains 5mM MgCl ₂, 0.5% glycine), 30 ℃, 250rpm reaches early stage stable growth phase behind the about 25hr of shaking culture, the muddiness that is creamy white, and a large amount of mycelia suspended substances are arranged.With bacterium liquid in 4 ℃, 3500rpm, centrifugal 15min collects mycelia, uses the lysis buffer washed twice, obtains the about 2.5mL of mycelia.Add 10mL lysis buffer (lysozyme 5mg/mL) in the 2.5mL mycelia, vortex adds achromopeptidase (Achromopeptidase) to 3mg/ml, mixing again to homogeneous.37 ℃ of water-bath 30min.Add the SDS of 0.1mL Proteinase K (20mg/mL is with the fresh preparation of lysis buffer), 1mL10%, put into 70 ℃ of water-baths behind the mixing rapidly, 15min to basic clarification, puts cooled on ice.The KAc solution that adds 2.5mL 5M, cooled on ice 15min.Add the saturated phenol of 15mL Tris, mixing adds the 15mL chloroform more gently, mixing gently, 20000rpm, 4 ℃, centrifugal 20min.Rifle head with cut places new centrifuge tube with the water sucking-off, adds isopyknic chloroform: primary isoamyl alcohol=mixed solution extracting in 24: 1, mixing gently, 12000rpm, 4 ℃, centrifugal 10min.Rifle head with cut places new centrifuge tube with the water sucking-off again, adds the dehydrated alcohol of 2 times of volumes, and mixing has the DNA of agglomerate to occur.Its hook is gone out, place new centrifuge tube, add the washing with alcohol of 5mL70%, liquid is inclined to, blot with rifle.Add 5mLTE dissolving (add the active RNaseA of no DNase to final concentration be 50 μ g/mL) again, 37 ℃ of water-bath 0.5hr.With isopyknic saturated phenol extracting twice, use isopyknic chloroform again: the mixed solution extracting twice of primary isoamyl alcohol=24: 1, add the NaAc solution of 0.1 times of volume 3M to aqueous phase, the dehydrated alcohol of 2 times of volumes, mixing has cotton-shaped DNA to occur gently.With 70% washing with alcohol DNA precipitation, sucking-off liquid.Add the 1mL absolute ethanol washing again, sucking-off liquid dries up in the super clean bench, is dissolved among the TE (pH 8.0) of proper volume.If be difficult to dissolving, can be stored in 4 ℃ at last at 55 ℃ of water-bath 2hr.

Embodiment 2

Promise card thiazole rhzomorph produces the structure of bacterium Nocardia bacteria Nocardia sp.WW-12651 genomic library:

At first determine the consumption of Sau3AI by a series of dilution experiment, a large amount of on this basis enzymes are cut the dna fragmentation that obtains and are slightly larger than 40kb, dephosphorization.Carrier pOJ446 cuts and dephosphorization in the middle of two cos sequences with HpaI earlier, and then cuts with BamHI from multiple clone site, obtains two connecting arms, is connected with the dna fragmentation that is about 40kb for preparing and spends the night.Take out package kit (PromegaPackagene Extract) from-80 ℃ and be put on ice, treat its lucky thawing, add the above-mentioned connection liquid of 5uL immediately, flick mixing, note not producing bubble, room temperature (about 22 ℃) is placed 3hr.Add 445uL Phage damping fluid, mixing turns upside down.Add the 25uL chloroform again, the mixing that turns upside down makes it slowly streak whole liquid with termination reaction, gently gets rid of with whizzer, makes chloroform be sunken to the bottom, is stored in 4 ℃.With test kit with the streak inoculation on the LB flat board of E.coliLE392 bacterial classification cultivate.Choose single bacterium colony and in 3mL LB, (add the MgSO of 30 μ L1M ₄The maltose solution of solution and 30 μ L 20%), 37 ℃, 250rpm, shaking culture is spent the night.The 500 μ L bacterium liquid of transferring again (add the MgSO of 500 μ L in the LB of 50mL ₄The maltose solution of solution and 500 μ L 20%), 37 ℃, 250rpm, shaking culture is to OD ₆₀₀=0.6-0.8.Get 2.5 μ L packing liquid, add 97.5 μ L phage damping fluids and 100 μ L E.Coli LE392 (OD ₆₀₀=0.67), mixing gently, 22 ℃ of water-bath 0.5hr.The LB mixing that adds 100 μ L again, 37 ℃, water-bath 75min is applied on the LB flat board and (contains Am 100 μ g/mL), and 37 ℃ of overnight incubation are to there being bacterium colony to grow.

Dull and stereotyped long 50000 clones of surpassing that have scrape with LB, add glycerine (final concentration 18%) and Apramycin (final concentration 50ug/ml), by every pipe 200uL packing, in-80 ℃ of preservations.From flat board, transfer 10 clones at random, be inoculated in the LB substratum and cultivate, prepare the extracting recombinant cosmid in a small amount by the alkaline process of escherichia coli plasmid.The HaeIII enzyme is cut evaluation, and detects with 0.7% agarose gel electrophoresis.According to the length of each dna fragmentation of electrophoretogram adduction, estimate that each glutinous grain inserts a segmental size and is about 35-40kb, and calculate tiring of library with this and be about 30000cfu/ μ g DNA.Because the size of most of actinomycetes chromosomal DNAs is about 8Mb, for inserting the library that fragment is 20kb, it is tired is that 2000～5000cfu/ μ gDNA just is enough to represent whole genome.According to above experiment, tire and reach 30000cfu/ μ g DNA in the library that we set up, and inserts fragment and be about about 40kb, and this library that shows that we set up has good quality, can satisfy the needs of library screening.

Embodiment 3

Promise card thiazole rhzomorph produces fermentation, product separation and purification and the evaluation of bacterium Nocardia bacteria Nocardia sp.WW-12651:

At first with 300 μ L-80 ℃ of frozen Nocardia sp.WW-12651 mycelia suspensions, be inoculated in (Zulkovsky starch 2%, glucose 0.5%, N-Z Case 0.3%, yeast extract 0.2%, flesh of fish extract 0.5%, lime carbonate 0.3%) in the seed culture medium of 25mL, 32 ℃, 250rpm cultivated 3 days.Therefrom get in the fermention medium that 2mL is transferred to 50mL (glucose 2%, HY-yeast 4121%, nutritious soy bean 1%), 30 ℃, 250rpm cultivated 4-5 days.Then fermented liquid is merged, transfer in the centrifuge tube, 3800rpm, centrifugal 15min discards the mycelia precipitation.Supernatant liquid merges organic phase with equal volume of ethyl acetate twice.Use anhydrous MgSO ₄Or anhydrous Na ₂SO ₄Drying is filtered, and 37 ℃ are evaporated to dried.Sample is dissolved in chloroform: in the mixed solvent of methyl alcohol=9: 1, whether there is Nocathiacins to have that (Nocathiacin I, II, III can send yellow-green fluorescence under long wave ultraviolet in the preliminary extract with TLC plate detection fermented liquid, TLC developping agent chloroform: methyl alcohol: formic acid=90: 10: 0.1), further can carry out biological activity assay (Nocathiacins can suppress the growth of S.ceolicolor M110, forms inhibition zone) with S.ceolicolor M110.

With the ethyl acetate crude extract of 2L fermented liquid, be dissolved in the mixed solvent of chloroform/methanol on this basis, behind the 100-200 order silica gel mixed sample, carry out column chromatography, elution requirement with 300-400 purpose silica gel: hexane/chloroform=1: 1,100ml; Chloroform 100ml; Chloroform/methanol=99: 1,100ml; Chloroform/methanol=98: 2,300ml; Chloroform/methanol=97: 3,200ml; Chloroform/methanol=95: 5,300ml; Chloroform/methanol=90: 10,200ml.Wherein in the component of chloroform/methanol=95: 5, detected the point of yellow-green fluorescence.Collect this component, 30 ℃ are evaporated to driedly, carry out the separation and purification of HPLC semipreparative column.

Detect wavelength: UV=220nm;

Pillar: Agilent ZORAX SB-C18 5 μ m 4.6 * 250mm, PN 880975-902, SN USCL024998, LN B07051;

Moving phase condition: v=1mL/min; A=H ₂O (0.1%TFA); B=CH ₃CN;

Time (min)	?0	??3	??6	??25	??27	??30	??32
								?B(％)	?0	??15	??40	??70	??90	??90	??15

Collecting the HPLC retention time is the component of 15min, carries out HPLC-MS (ESI) and identifies, is Nocathiacin I, corresponding [M+H] ⁺Molecular ion peak is m/z=1437.3.Simultaneously we also and have carried out HPLC-MS (ESI) and have identified, corresponding [M+H] to components such as NocathiacinII, III, MJ347-81F4-B with similar approach separation and purification from the fermented liquid of Nocardia sp.WW-12651 ⁺Molecular ion peak is followed successively by m/z=1421.3,1266.2,1368.3.

Embodiment 4

The biosynthesis gene of PCR clone promise card thiazole rhzomorph:

The PCR system comprises: and DMSO (8%, v/v), MgCl ₂(1.5mM), dNTP (0.2mM), merger property primer (0.2 μ M), Taq archaeal dna polymerase (2u) and the total DNA of an amount of template Nocardia sp.WW-12651.At first 95 ℃, 5min, 1 takes turns; 94 ℃ then, 1min, 63 ℃, 1min, 72 ℃, 1min, 10 take turns; 94 ℃, 1min, 55 ℃, 1min, 72 ℃, 1min, 20 take turns; Last 72 ℃, 10min, 1 takes turns.After PCR finishes, 1.5% agarose electrophoresis check result.Low melting point glue reclaims the dna fragmentation of expection size, with the EcoRV digestion of carrier pSP72, the 2.4kbDNA fragment of CIAP dephosphorization connects, transformed into escherichia coli DH5 α competent cell, be coated on and contain on the suitable antibiotic LB flat board, 37 ℃ are cultured to transformant and grow.Picking list bacterium colony overnight incubation in the liquid LB, extracting plasmid, Bgl II and EcoRV double digestion identify that the DNA that whether contains the expection size inserts fragment.And the plasmid that will be inserted with the big or small dna fragmentation of expection checks order.

Embodiment 5

Making nucleic acid molecular hybridization:

1) DIG dna marker: DNA to be marked is diluted to cumulative volume 15 μ L with sterilized water, and heat denatured is 10 minutes in the boiling water bath, places cryosel to bathe cooling immediately.Then add Hexanucleotide Mix (10 *) 2 μ L, dNTP Labeling Mix 2 μ L, Klenow enzyme labeling grade 1 μ L, after mixing, about 16 hours of 37 ℃ of water-baths.Add 0.8 μ L 0.8M EDTA (pH8.0) with termination reaction, add 2.5 μ L 4MLiCl, mix, add the DNA behind the dehydrated alcohol precipitation mark of 75 μ L precoolings again, place-80 ℃ of sedimentations 40 minutes.4 ℃, 12000rpm collected DNA in centrifugal 20 minutes, and the 70% washing with alcohol DNA precipitation with precooling is dissolved in 50 μ L TE (in (pH 8.0) again after the vacuum-drying.

2) quality examination behind the DIG dna probe mark: the dna probe of dilution mark is to following six gradients, 1,10 ^-1, 10 ^-2, 10 ^-3, 10 ^-4, 10 ^-5The contrast DNA of dilution mark is respectively to following concentration 1 μ g/mL, 100ng/mL, 10ng/mL, 1ng/mL, 0.1ng/mL, 0.01ng/mL.The DNA sample spot of getting the above-mentioned concentration of 1 μ L respectively is on the nylon membrane of hybridization usefulness, according to 7) described step carries out color reaction, and the colored intensity of the contrast DNA of the dna probe of contrast marker and DIG mark is with the dna probe concentration of decision mark.

3) film of colony hybridization (library screening) shifts: therefrom get 50 μ L, add 450 μ L LB dilution and obtain 10 ^-1Extension rate, doubling dilution obtains 10 again ^-2, 10 ^-3, 10 ^-4, 10 ^-5, 10 ^-6Therefrom get 300 μ L respectively and be coated with the LB flat board that a block specifications is 15cm * 15cm (containing apramycin 50 μ g/mL).37 ℃ of overnight incubation are to there being bacterium colony to grow.Choose suitable Dilution ratio, make every dull and stereotyped about 1200-1500 clone.According to selected dilution proportion library, evenly be coated with four flat boards, 37 ℃ of overnight incubation with LB.Big or small clip nylon membrane according to flat board is covered in planar surface carefully and does not produce bubble, carries out position mark, takes off nylon membrane after 1 minute and places on the dry filter paper, is combined on the nylon membrane until bacterium colony in dry 10 minutes.The primary flat board places incubator 4-5hr, and the clone is regrowed as former flat board.Nylon membrane is placed sex change liquid (0.25MNaOH, 1.5M NaCl) saturated last 15 minute of filter paper (not soaking film), be transferred to neutralizer (pH 7.5 for 1.0MTris.HCl, 1.5M NaCl) saturated last 5 minute of filter paper.Be transferred to 2 * SSC (20xSSC storing solution (L ^-1): NaCl, 175.3g, Trisodium Citrate, 88.2g, pH=7.0) natural air drying on the saturated filter paper.Take off nylon membrane and place baking oven, fix 45 minutes for 120 ℃.In 3 * SSC/0.1%SDS solution, vibrate under the normal temperature and washed 3 hours, to remove cell debris.

4) film of Southern hybridization shifts: DNA sample electrophoresis on the sepharose of proper concn is carried out mark to suitable distance.Be soaked in depurination 20min among the HCl of 400mL 0.25M, make the tetrabromophenol sulfonphthalein flavescence, wash for several times with deionized water.Immerse (NaOH 0.5M, NaCl 1M) 15min in the ealkaline buffer under the room temperature, and vibration gently.Continue to soak gel 20min after changing ealkaline buffer, and vibration gently, it is inferior to give a baby a bath on the third day after its birth with deionized water.Get every limit all than the nylon membrane of the big 1mm of gel, soak fully, carry out mark with deionized water.Adopt upwards capillary transfer method, with the transfering buffering liquid transfer 8-24hr of 10 * SSC.Wash film slightly with 2 * SSC, 120 ℃ of baking 30min.

5) prehybridization and hybridization: preheating hybridization solution (20mL/100cm ²) to 68 ℃ of hybridization temperatures, put into the hybridization nylon membrane, vibrate gently and be incubated 30 minutes.With the sex change 5 minutes in boiling water bath of the dna probe of DIG mark, place cryosel to bathe cooling immediately.After the cooling, with the DIG hybridization solution (2.5mL/100cm of dna probe and suitable volumes ²) mix.Remove prehybridization solution and immediately dna probe/DIG hybridization solution is added, vibration keeps 64 ℃ of hybridization temperatures or 68 ℃ about 16 hours gently.

6) the tight wash-out in hybridization back: under the room temperature with 2 * SSC/0.1%SDS rinsing twice, each 5 minutes.68 ℃, with 0.1 * SSC/0.1%SDS vibration rinsing twice, each 15 minutes.

7) color reaction and detection: the nylon membrane behind the tight wash-out is at lavation buffer solution (0.1M toxilic acid, 0.15M NaCl, pH=7.5,0.3% (v/v) Tween 20) middle balance 1-5 minute, then (closed reagent is dissolved in the 0.1M toxilic acid with 10% concentration at the sealing damping fluid, 0.15M NaCl, pH=7.5) middle sealing is 30 minutes, soaks 30 minutes in antibody then.Behind twice of lavation buffer solution rinsing nylon membrane, with detecting damping fluid (0.1M Tris-HCl, 0.1M NaCl, pH=9.5) middle balance 2-5 minute, [NBT (nitroblue tetrazolium chloride) is dissolved in 70%DMF at last nylon membrane to be placed the new chromophoric solution of preparing of 10mL, concentration is 70mg/mL, and BCIP (5-bromo-4-chloro-3-indolyl-phosphate) is water-soluble, and concentration is 50mg/mL.Add 45 μ L NBT in the time spent 10mL chromophoric solution, 35 μ L BCIP], place dark to develop the color.Develop the color the suitable back rinsed with deionized water of using with termination reaction.

Embodiment 6

Acquisition and the tunning analysis of the complementary mutant strain of allos:

At first produce in the system of bacterium Streptomyces actuosus ATCC25421 the establishing target gene with the mutant strain of frame disappearance at nosiheptide.Used carrier is the plasmid pKC1139 that contains the temperature sensitive type replicon, with being used for of building plasmid with the frame disappearance, import in the generation bacterium of nosiheptide by engaging the method (as follows) that shifts between E.coli S17-1 and Streptomyces actuosus ATCC25421 genus, cultivated 4-5 days the zygote that screening has the Am resistance for 30 ℃.Then the zygote that obtains is inoculated in the TSB liquid nutrient medium (apramycin 50 μ g/ml) 30 ℃ shaking culture 2-3 days.Coat again on the MS flat board that contains apramycin 100 μ g/ml, make it to take place single cross 42 ℃ of integration and change.The single cross that obtains is changed mutant strain 30 ℃ of lax cultivations (not adding apramycin) of carrying out the 10-20 wheel, obtain mutant strain by resistance screening again the apramycin sensitivity.The total DNA of extracting carries out the PCR screening, obtains to take place the mutant strain of double exchange.And the double exchange mutant strain that obtains is carried out the PCR order-checking on genotype, verified taken place really with the frame disappearance, and internal gene not to have sudden change.Detect by fermentation and LC-MS then, on phenotype, verified, no longer produce nosiheptide, just obtained the mutant strain of target gene with the frame disappearance.

On this basis, with intimate gene in the promise card thiazole rhzomorph biological synthesis gene cluster and the erythromycin promotor ErmE that comes from pLL6212 ^*Be cloned in the corresponding site of integrating vector pSET152, obtain being used for allos complementary plasmid.The allos complementary plasmid that is used for that builds is imported to the mutant strain of nosiheptide corresponding gene with the frame disappearance by engaging the method that shifts between belonging to,, obtain the complementary mutant strain of allos through the apramycin resistance screening.The mutant strain of gained ferments and the LC-MS detection after verifying on the genotype, recovers to have produced nosiheptide, and the function that these genes are described is consistent.

E.coli S17-1 and nosiheptide produce bacterium Streptomyces actuosus ATCC25421 and as follows with engaging the method that shifts between frame deletion mutantion strain genus:

Picking list colony inoculation overnight incubation to the test tube from the intestinal bacteria culture plate that contains suitable plasmid is drawn 200-300 μ l bacterium liquid and is transferred among the 20ml LB, places 37 ℃ of shaking tables to be cultured to OD ₆₀₀Be 0.3-0.4.With the centrifugation of bacterium liquid,, use the LB of 2ml resuspended then, as the intestinal bacteria donorcells with isopyknic LB washed twice.Get the frozen Streptomycesactuosus ATCC25421 that preserves in-80 ℃, 20% glycerine of 50 μ l or with the spore suspension (2-3x10 of frame deletion mutantion strain ⁹Individual/as ml), to use H ₂O dilutes 10 times to 500 μ l, uses isopyknic TES damping fluid (0.05M, pH 8.0) washed twice then, is resuspended in isopyknic TES damping fluid, and 50 ℃ of heat shock 10min make spore germination.Add isopyknic TSB substratum then, 37 ℃ of temperature were bathed centrifugal being resuspended among the 500 μ l LB as the streptomycete recipient cell 3-4 hour.The recipient cell 100 μ L of different concns are mixed with isopyknic donorcells, directly be coated on and contain 10mM MgCl ₂IWL-4 (Soluble Starch 10g/L, K ₂HPO ₄1g/L, MgSO ₄1g/L, NaCl1g/L, (NH ₄) SO ₄2g/L, CaCO ₃2g/L, Yeast extract 0.5g/L, tryptone1g/L, FeSO ₄7H ₂O0.001g/L, MnCl ₂7H ₂O 0.001g/L, ZnSO ₄7H ₂O 0.001g/L, agar powder 20g/L, pH=7.2) or AS-1 (Yeast extract 1g/L, L-alanine 0.2g/L, L-arginine 0.5g/L, SolubleStarch 5g/L, NaCl 2.5g/L, Na ₂SO ₄10g/L, agar powder 20g/L pH=7.5) on the flat board, cultivated 12-16 hour for 30 ℃.Wash planar surface gently with the most of intestinal bacteria of flush away with sterilized water, contain nalidixic acid (final concentration is 50ng/ μ L) and corresponding antibiotic sterilized water at each dull and stereotyped surface coverage 1mL then.Cultivate picking zygote more than 5 days for 30 ℃.

Nosiheptide produces bacterium Streptomyces actuosus ATCC25421 and the fermentation of mutant strain and the Analysis and Identification method of tunning:

The spore suspension of getting 100ul Streptomyces actuosus ATCC25421 or mutant strain is inoculated into 50ml seed culture medium (Sucrose 20g/L, corn steep liquor 30ml/L, peptone 5g/L, CaCO is housed ₃5g/L; PH 7.0) the 250ml conical flask in, 30 ℃, 270rpm cultivated 24-48 hour, switching 10ml mycelia suspension is to 50ml fermention medium (Glucose 30g/L, Cotton meal 10g/L, NaCl 3g/L, 2x trace element 5ml/L, CaCO are housed ₃3g/L; PH 7.0) Erlenmeyer flask in, 28 ℃, 270rpm cultivated 96-120 hour.

The bacterium liquid that ferments is centrifugal, and supernatant discarded adds the THF of proper volume in mycelia precipitation, stir 30min, and suction filtration is removed solid precipitation, collects organic phase, be spin-dried for pressed powder, be dissolved among the THF of proper volume.

Get 20 μ l and carry out the HPLC-MS detection, detect wavelength: UV=220nm; Pillar: Agilent ZORAXSB-C18 5 μ m 4.6 * 250mm, PN 880975-902, SN USCL024998, LN B07051; Moving phase condition: v=1mL/min; A=H ₂O (containing 0.1%HCOOH); B=CH ₃CN (containing 0.1%HCOOH);

Time (min)	?0	??3	??6	??12	??19	??22	??28	??30
									?B(％)	?0	??15	??40	??40	??55	??85	??85	??15

Embodiment 7

Acquisition of heterogenous expression mutant strain and tunning analysis:

With target gene in the promise card thiazole rhzomorph biological synthesis gene cluster and the erythromycin promotor ErmE that comes from pLL6212 ^*Be cloned in the corresponding site of integrating vector puSET152, obtain being used for the plasmid of heterogenous expression.The plasmid that builds is imported among the generation bacterium Streptomyces actuosus ATCC25421 of nosiheptide by engaging the method that shifts between belonging among the embodiment 6,, obtain the heterogenous expression mutant strain through the apramycin resistance screening.By genotype checking correct after, refer again to fermentation among the embodiment 6 and detection method and carry out analysis on the phenotype, the analog that detects the new nosiheptide that produces by LC-MS is inferred the function of target gene.

Following gene that content provides according to the present invention and protein sequence:

Amino acid/nucleotides sequence tabulation:

SEQUENCE?LISTING

＜110〉Shanghai Organic Chemistry Institute, Chinese Academy of Sciences

＜120〉biological synthesis gene cluster of promise card thiazole rhzomorph (Nocathiacins)

＜130〉specification sheets, claims

<160>1

<170>PatentIn?version?3.3

<210>1

<211>45560

<212>DNA

＜213〉Nocardia bacteria Nocardia sp.WW-12651

<400>1

GCTGCAGCGG?CCGCACTAGT?GGATCCCGAA?ACCGGACACC?GCGGCGCGTC?TCGGCCTGCC????60

CAGCTCCGGC?CACGGCCGAG?CCTCGGTCAG?CAGCGACACC?GCGCCCGCCG?ACCAGTCCAC???120

CGCCTGCGAT?GGCGCGTCGA?CATGCAGGGT?CTTGGGCATG?ACCCCGTTGC?GCAGGGCCAT???180

CACCAGCTTG?ATGACGCCGC?CCACGCCTGC?GGCGGCCTGC?GTGTGGCCGA?CGTTGGACTT???240

GAACGAGCCC?AGCCGCAGCG?GCTCCTCGCG?TTCCTGGCCG?TAGGCGGCCA?GCAGTGCCTG???300

CGCTTCGATC?GGGTCGCCGA?GCCTGGTGCC?AGTGCCGTGC?GCGTCCACCA?GGTCCACTTC???360

GGATGGCGAG?AGTCCGGCGT?CGGCCAGCGC?CTGGCGGATG?ACCCGCTGCT?GTGACGGGCC???420

GTTGGGGGCG?GTGAGCCCGT?TGGACGCGCC?GTCGGAGTTC?ACCGCGGAGC?CGCGCACGAC???480

GGCCAGCACC?GGGTGCCCGT?TGGCGAGCGC?GTCGGAGAGC?CGTTCCAGGA?CGACGAACCC???540

GGCCCCCTCC?GACCAGCCCG?TGCCGTCGGC?CGCAGCGGCG?AACGCCTTGC?ACCGGCCGTC???600

GGCGGACAGG?CCACGCTGGC?GGGAGAACTC?GATGAACGTG?TCCGGCGTCG?GCATGACGGT???660

GGCCCCGCCC?GCCAGCGCCA?GCCCGCATTC?GCCGCGGCGC?AGCGCCTGCA?CGGCCAGGTG???720

CACGGCGACC?AGCGACGACG?AGCAGGCCGT?GTCGACCGTC?ATCGACGGCC?CTTCGAGGCC???780

CAGGGTGTAG?GAGACCCGGC?CGGAGGCGAC?GCTGGCCGCG?CCACCGGTCA?CCCCGAAGCC???840

CTCACCGCCC?TGCTCGTCCG?CGCCGAGCCC?GTAGCGCTGG?CCGCGGTGGC?CCATCAGCCC???900

GGCGTAGACG?CCGGTCGCGG?TTCCCCTGAG?CGAGCGCGGA?TCGATCCCGG?AGCGCTCCAG???960

CGACTCCCAC?GCGGTCTCCA?GCAGCAGCCG?CTGCTGCGGG?TCCATCGCCA?GGGCCTCGCG??1020

CGGGGAGACC?CCGAAGAAGC?CCGCGTCGAA?CCCGGGGGCG?TCGTGCAGGA?AGCCCCCGCC??1080

GCGGGCGTAG?TAGCGGCCGG?GCAGTCCGGG?TTCGGGGTCG?AAAAGGCCGT?CGACATCCCA??1140

GCCGCGGTCG?CGCGGGAACT?CCCCGATCGC?GTCCCCGCCG?GAGGCGACGA?GCTCCCACAG??1200

CTGCTCCGGC?GTGCCGACGC?CACCGGGGAA?CCGGCAGGCC?ATGCCGACGA?TCGCAATGGG??1260

CGCTCCCTGC?ACATCGCGCA?GCTTGTCGCG?CGCCTCCTGC?AGCTCGGAGA?CCGCGCGCCG??1320

GAGGTAGTCC?CGGAGCTTGC?CCTCGTTCTC?CATCGTGTCG?CAACCCCCTG?CTGACCGGTG??1380

ACAGGCGCCA?ATGGCCAATC?CAACCGGGGC?AGCAGGCGGT?GCGGCGGTGC?TGCGGAACCA??1440

ATTCCGGACC?GGGAAACTGG?TCTCCCGTCA?AGGGCGGGGA?GACCGGTCAC?CGCGGATATG??1500

ATGCTCGGGC?TGAGGTCAGG?AGACCCGGGT?CGCGGCGGCC?GGGGTCGGGA?ACCCCTCGGG??1560

CAGGTCGTCC?AGGGTCATCG?TGGTGATGTG?CGGTCTGCCC?GCGCCCCATT?CGGGCCTGCG??1620

CAGGAACAGG?CCGGGGTCGG?CGGCGGCCAC?CACCAGCAGC?GGTGCGGTCG?CAGGCGGGTC??1680

GAGCAGCTCC?TCGACGAAGT?CGAGCATGGC?GTCGTCGGCC?AGGTGCAGGT?CGTCAGCGAG??1740

CACCACGAGC?GGGCGGGGCG?CGGCCAGCCC?GGCCACGACC?GTCCACCAGT?CGGCCACCAC??1800

CGACTCCTCG?GTGTGGCAGG?TCGAATCCGG?CTCGACGAAC?GCGCGCAGCC?GGGACAGCAC??1860

GCCCGCGGCG?GTGCGGCGGT?CGCCCACCAC?GCCGCGCACC?GCACGGTGCA?GCTTGTCCCT??1920

GGCCACGTCG?CGGCTGTCCT?CGCCGCCGAC?CCCGCAGCAG?GCGAACAGGA?TCTCCCCGCG??1980

CAGCCGCGCC?GTGGTCGCGA?GCACGCGGCC?GGTCAGCCTC?GGGCCGATCG?CCGCGATCCG??2040

GCTCGCACGC?CGTTCAAAAG?CCGAGAGCAG?CCACGACTTG?CCCATCCCCG?GGCCACCGAG??2100

CACCGACACC?AGGTGCGGTC?GTCCCCGGCT?GCGGACGCGT?TCCAGAACGC?TGTCCAGCAC??2160

GTCGAGTTCC?GGCCTGCGGT?CCACCGCCAC?CATCCTCGGG?TGGATGCCCG?CCCCGATCAG??2220

CTCGCGGGTG?CGTTCGCAGA?CGGCGATCTC?GTTGGTGTCG?GCGGCCAGCA?CCAACGTCTC??2280

GGACTCCACC?AGCAGCGCGC?CGCCGATGTC?GAGGGCGTCG?GTCACGTCCG?CGGGCGGCTC??2340

CCCGGTGACC?ACGGCCACCC?GCAGCACGTG?CCGGGCGTGG?TGCGGGGACG?CCGAGAAGCA??2400

GAGCCGGTCG?CGCAGGGCGA?CGGCGGCGCG?CACCGCGCGC?TCAGCGCAGC?TCGCACGGTC??2460

GGGTTCGTCC?CGGAAGACAG?CCAGCGACAT?GGTTCCCATC?GACTGGGTGA?GGGTGCCGCC??2520

GAACAGCGTC?ACCTCCTCCG?CGACCGCGGC?GATGACGTCA?GCGAGCACAC?CGTCGACGGC??2580

CGACCGCGCG?CTTGGCCCGA?CCTCCACCCC?GATGAGGATC?GCGCTGACCC?TGCCGGGCCG??2640

CTGCGGCCTC?GGGGCCAGCC?GAACCGGCGC?CGTGTCCGAC?GCAGGCGCCT?CGTCCAACGG??2700

CCGCGGGCCG?AGGACCAGCG?CCGGGTCGTG?GGCGAGGATC?GCGTGCTGCA?ACACCCGCAG??2760

GTCCCGCCCT?GGCTCCAGGC?CGAGCGTGCC?GACCAGGGCC?GAGCGCACCC?GCTGGTAGAC??2820

GGCGAGCGCG?TCGGCCTGCC?TGCCGCTGCG?GTAGAGCGCG?AGCATGAGCT?GGCGGCCGAG??2880

CCGTTCGCGC?AGCGGTTCCG?ACTCGGCGAC?GGCGGTCAGC?TCGGCCAGCA?CGGCGAGATG?2940

CCTGCCGTTC?GCCAGTTCCG?CCTCGAAGTA?GTCCTCCATG?ACGTCGAGCC?GCAGGTCCTG?3000

CACCGCGGTC?AGCTCGGCCC?AGTCGTAGCC?GTCCTCCACC?AGGTCGGCGA?GGGCGGGACC?3060

GCGCCACAGG?GCCAGCGCGG?AGCGCAGGAT?CTTGGCGGCG?GTCTTCGTGT?GGCCCTCGGC?3120

GAGTTCGGCC?CTGCCCTGCT?CGGCGAGCTG?CTGGAACTGG?AACAGGTCGA?CCCGTTCCGG?3180

CTCCATGCGC?AGCACGTACC?CGGGCGACTG?GGTCAACAGC?CTCGGCGAGC?CTCCGTGGTT?3240

TCCGGCGAAC?ACGACACGCA?GCCCGCGCAC?CGCGTTCTGC?AGCACCTTGC?GTGCCGTCGG?3300

CGGCGCGTTG?TCCTCGCCCC?ACAGCCCGTC?CAGCAGCGCG?CTCGTGGGAA?CGGCTTTGTT?3360

GACATGCAAC?AAAAGCATCC?CGAGCGTGGC?GCGCTGGCGG?CTGCCGCCGA?GCTGAACCGG?3420

TTGGCCGCCG?CCATCGGCCT?CCAGCGGGCC?AAGAACCCGA?AAATGCATTC?GTCCCCCCGC?3480

GCTCACGTCG?CCGTGCCCCC?GCACGCGGCC?CGCGCTGTCA?GGCTGAGGAC?CACTCGACAG?3540

GCGCTTCACC?ACCGGTGTGC?GGTTCGGGCG?CGAACACCGT?CATCGTGGTC?GGCGCCGCCT?3600

GGGGCGACGG?GACCAAGTGC?AGGTATTCGA?TCTCCACCCC?TACTGTGCCG?GCATCCGCAC?3660

CGCTCGTGTC?AAACCCGGTC?AGGCAGCCGC?AGTCCGCCTG?CTCGAAGCCC?GCGAATCGGT?3720

AGGCGACCTC?CATCATCCGG?TTGCGGTCGG?TCCTGCGGAA?GTCCGCCACA?AGGTGGGCCC?3780

CGGCGCCAGC?GGCCTGATCG?GTGAGCCAGC?GCAGCAGCAC?GGTGCCCGCG?CCGAAGGAGA?3840

CGACCCGGCA?CGAGGTGGCC?AGCAGCTTCA?GCCGCCACGC?CGCGTCGCCG?CGCTCGACGA?3900

GCATGACCCC?GACCGCGCCG?TGCGGGCCGA?ACCGGTCGGT?GAGCGAGATC?ACCAACACGT?3960

CGTGGCGCGG?GTCGGAGACG?AGCGCGCGCA?GGTCGGCGTC?CGAATAGTGG?ATTCCGGTGG?4020

CGTTCATCTG?GCTGGTGCGA?AGGGTCAGCT?CCTCGACCCT?GGACAGGTCC?TCCTCACGGG?4080

CCGTCCCGAT?GCGCATGACC?AAGTCCAGCG?TGCGCAGAAA?GTCCTCGTCC?GCGCCCGCGT?4140

GCTCCTCGCG?CTCTGCGTCG?CGGCGGAAGC?CCGCCTGGTA?CATCTCGCGG?CGCCTGCGCG?4200

CGTCGACGGT?CACCACCGCA?GGGCTGAAAT?CGGGCATATG?CGGCAACTGT?TCGGCCTGCG?4260

TCGCGTCGAA?GCAGCGCACC?TCGGGCAGGT?GGTGGGCCAC?CTCGGCGCGC?TCGGTCGGCA?4320

GGTCGTCGAT?GAACGCAATG?GTCTTCAGCG?CGAAGTTCAG?CTCCGCGGCG?ATCTCGCGCA?4380

CCGAGTTCGA?TTTGGCGCCC?CAGTGGATGC?GCGGCAGCAC?GAAGTACTCA?GCCACGCCCA?4440

GCCGCTCCAG?CATGGCCCAC?GCGTGGTCGT?GGTCGTTGCG?GCTGGCCACC?GATTGCAGGA?4500

TGCCGCGCGC?ATCCAGTTCC?ACGATGGTCT?TGCGCACGGC?ATCGCTGAGG?CGGACCTCGC?4560

CGTCCTCCAG?CAGGGTGCCT?CGCCACAGCG?TGTTGTCCAG?GTCCCAGACC?AGGCACTTCA?4620

CGACAGGGTG?GTCGGACATG?ATCGTCTCCC?CCGATCAGGG?GGCAGCGGCT?TCGGCCAGGA?4680

TCAGCTGGCT?GATCTCGGTG?CTGCCCTCGA?TGATCTCCAT?GAGTTTGGCG?TCGCGGTAGG?4740

CGCGCGCCAC?CACGTGCCCG?TCCGCCGCGC?CCGCCGAGGC?GAGCACCTGC?ACCGCCGAGG?4800

CAGCACCGCG?CGCCGCACCG?CCCGAGGCGA?CGTGCTTGGC?CAGCACCGCG?GCGATCGCCT?4860

GCCGCGGCGA?TCGCTCGTCC?CATGCGGCAC?TGGCCTCGGC?GCAGGTGTAG?GTGGCCGAGC?4920

GCTCGGCGGC?GTACAGCTCG?GCCACGTGCC?GGGCCACGAG?CTGGTGCTCC?AGCAGCCGCG?4980

TGCCGAACTG?GACGCGGGAG?CCCGCGTGCT?CGACCGCCGC?GCGCAGGCAC?GCGCGCAGAA?5040

TTCCGACGCA?GCCCCAGGCG?ACCGACAGCC?GCCCGTAGGT?CAGGGCGATG?GTGGTCAACA?5100

TGGTGACCGG?CTGGCCCGCG?GCGGCCAGCA?CGGCGTCTGC?TGGCAGCCGC?ACGCTGTCGA?5160

GGGTCACCGT?GGCGTGGCCC?GCCGCCCGAC?AGCCCATCGG?CTCGGGCACG?CGGTCGATCC?5220

GCACGCCGGG?GGCATCGGCG?GGAACCACGA?CCGCGGCGGC?GCCGTTTCCG?TAGCGGCCGA?5280

AGACGACAAC?CAGGTCGGCG?TAGCAGGCCG?CGGTGATCCA?GGTCTTCACC?CCGTCGACGA?5340

CGACGTCGTC?GCCGTCCTGG?CGAATCGTCG?TGGCCATCGC?GGCCAGGTCG?CTGCCCGCCC?5400

CCGGCTCGCT?GAAGGCGACC?GCCGCCAGCG?ACCCGCCGGT?CAGCGCGGCC?AGGTGCGTGG?5460

CCCGCTGGAC?GCGGTCGCCG?AGGCGCTGGA?TCGTCCAGGC?CGCCATGCCC?TGCGAGGTCA?5520

TGACGCTGCG?CAGCGAGCTG?CACAGGGCCC?CGGTGTGCGC?GGTCAGCTCC?CCGTTGTCCA?5580

CACCGGACAG?GTCGAGACCG?CCGTGCTCGG?CGGCGACCTC?GGCGCACAGC?AGGCCCTTGG?5640

CACCCAGCCC?GCGCAGCACG?TCGACCGGGA?TCTCACCCGC?GACGTCCCAC?TCCCCCGCCG?5700

CGTCGCCCAC?CGTCTCGGTG?ACGAGCGCGG?CCAGGTCAGA?CACCGGAGGG?CTCCACGCGC?5760

AGCCGGGTCA?CCAGCGCGCT?CATCGCGCGC?ACCGTCCGGA?AGTTGTCCAG?CGCCAGGTCC?5820

GGTCCCTCGA?CGGCGATGTC?GAACGCGCCC?TCCACGAACA?CGACCAGCTC?CATCGTGAAC?5880

AGCGACGACA?CCACGCCGGA?GGCGAACAAG?TCGACGTCGG?GTTCCCACAC?CACCTTGGTC?5940

TTGGCGGTCA?GGAACTCCAC?CAGCTGCTCC?TCGATCGCGT?ACGTCGTCAG?GGACGTCATG?6000

CTTCCTCCGC?TCAGATCGGG?TTCTTGCGGG?CCAGGGTGAT?CCCGTCGGCC?ATCGGCAGCA?6060

GGCACAGCTC?GACCCGGTCA?TCGGCGCGCA?GCGCGGCGTT?GAGCCCGCGG?ATCGCGGTCG?6120

TGTCGGCGTC?CTGGGCGTCC?GGGTCTACGA?CGCGGCCGAA?GAACAGGGTG?TTGTCCAGCA?6180

CCGCGAGACC?GCCCGGCCGC?AGGTGAAGCA?GCGCTTGCTC?GTAGTAGGTC?GGGTACCCGG?6240

CCTTGTCCGC?GTCGATGAAG?ACGAGGTCGA?ACGACCCCGG?ACCACGCTCG?TCGAGCAGAT?6300

CCGCCGCCGT?CCGCGCCCCG?TCCCCGACCC?GCAGGACCAC?CCGGTCCGCC?ACCCCGGCGC?6360

GCTCCCAGTA?GCGCCGGGCG?ATCCTGGTCC?AGCGCTCGCT?GATGTCGCAG?GTCACCACTC?6420

GTCCGCCTGG?CGGGAGGGCA?CGGGCCATGC?ACAGCGTGCC?GTAGCCGGTG?AACGTGCCCA?6480

GTTCCAGCAC?TTCCCGCGCG?CCGGTCAGCC?CGACCAGCAT?GGCCAGCAGC?TGGCCCTGCT?6540

CTGGCATGGT?GACCATCGCC?GCCAGCGCGG?GCATCGCCTC?GGTCTCGGCG?CGCAGGTCGC?6600

GCAGCAGGTC?GTCCTCGCGG?ACGGACACCG?CGCGCACGTA?CTCCACGAGG?TCGTCGGTGA?6660

GCTGGACCTG?ACCCGCCATC?AGAGGGCCCC?GTACTCGTAG?AACCCGCGCC?CGGTCTTGCG?6720

GCCGTGGTGG?CCGTCGGCGA?CCTTGCGCAG?CAGCAGCCCG?CTCGGCTTGC?AGCCCTCGTC?6780

CCCGGTCCGC?TCGTAGAGCA?CCCGCAAGGA?GTCGACGAGG?TTGTCGATGC?CGATGAGGTC?6840

GGCGGTCTTC?AGCGGACCGG?TGCGGTGGCC?GATGCAGTGC?TCCATCAGCG?CGTCCACGTC?6900

CTCGACGCTG?GCCCTGCCCT?CCTCGACCAC?CCTGGCCGCG?TCGTTGATCA?TCCGGTGCAG?6960

GACCCGGCTG?GTGACGAAGC?CAGGGCCGTC?GTTGACCACG?ATCGCCTTGC?GTCCCAGCCG?7020

CTCCAGCAGC?GCGCGCACGG?CGACCATCGC?CGCGTCCCCG?GTGCGCGGTC?CGCGCACGAC?7080

CTCCAGCGTC?CCGATCAGGT?ACGGCGGGTT?CATGAAGTGC?ACCCCGACCA?GGAACTCCGG?7140

CCTCGGCACG?TGCCCGGCCA?GCTCGTCGAC?CGGGATGGAG?GAGGTGTTGG?TGATGCGCAG?7200

CGCATCCGGG?GCGACGACGG?CGGCGATCTC?GTTCTGTGCC?TTGACCTTCA?GCTCGGCTGT?7260

CTCGGTGATC?GCCTCGACGA?CGACCCCCGC?GCCCGCCGCC?GCGTCGACCG?AGTCGGCGAG?7320

GTCCAGGTCG?CCGATCGGGC?CGTGTCGGGG?GAGCGCGCCG?AGGACGTGGG?CCAAACGCAG?7380

CTCGTGCCGC?ACCCGCTTGC?GCGCGGTGGC?CAGCCGCTCC?TCATCGACGT?CCACCAGGGT?7440

CACCTGGACG?CCGCGGCCGA?TCGCAAGAGC?GGTGATCCCC?ACCCCCATCA?CTCCGGCGCC?7500

GAGCACCGCG?AGCCGGTCGG?TCATGCTTCC?CCCTCGGATG?CGTGGTGTGC?CCGGTCAAAT?7560

GAACACCACG?CGGCGCGGGC?GGCGAGTGCG?CCTGCGCACC?AAATCGGGCC?TCGGGTTCTA?7620

GCCCCCGGTT?CCAGTACCGC?CCGCCGCGGG?CCGACCTACC?CTGCGAGCAC?ACCGCGAGTG?7680

AGGAGCGCCA?TGCCAGACAT?CGATCCGGCA?CACTTCCGGC?GGACCCTCGG?CTACCTCCCC?7740

ACCGGCGTCA?CCATCGTCAC?TTCCACCGAC?GCGCGCGGTC?TGCCGGTGGG?CTTGGCCTGC?7800

AACTCGATCA?CGTCGGTGTC?CCTCGACCCG?CCCCTGGTGC?TGGTGTGCGC?GGCCAAGTCG?7860

TCGTCCACCT?GGCCCACCAT?CCGGCGGAGC?GGCACGTTCA?CCGTCAACGT?CCTCGACCGC?7920

GCGGGGGAAC?GGATCTGCCG?CCGCTTCGCC?GCCCGCGGCG?TCGACCGCTT?CGCCGGAACT?7980

CCCTGGACCC?CGGCCCCCAC?CGGCCCCGAG?CTGGACGAGG?CCCTGGCCTG?GATCTCCTGC?8040

GTCATCCACG?CCGAACACGA?CGCGGGCGAC?CACGTGATCG?TCATCGGCCG?GGTCACCCGC?8100

CTCCTGCACT?CGCCCCTCTC?CGGCCCGCCG?CTGGTCTTCC?ATCGCGGACG?CTACGGCTCC?8160

TTCGCCCAGT?CCGCCGTCGT?CCCGGTGCCC?GGCCTCATCT?GACCGAGCGC?CGCGAAGAAA?8220

TCTTGGACGG?CGATGTCGAG?AACCGGGGGC?CTGCTCCGTC?CTCGGGGTGA?CTGCGGCCAG?8280

AATGGGCCGC?ACCAGCACGA?GGAGAACCAC?GATGGCCAAG?TACCTGCTGC?TCAAGCACTA??8340

CCGGGGCGCC?CCGGCCGCCG?CCAACGACGT?GCCGATGGAC?CAGTGGACCC?CGGAGGAGAT??8400

CACGGCGCAC?GTGCAGTACA?TGCGCGACTT?CGCGGCCCGG?CTGGAGGAGA?GCGGCGAGTA??8460

CGTCGACGGC?CAGGCGCTCG?CCCCGGAGGG?GATGTTCGTC?CGCTACGACG?GCGAGGGGCG??8520

TCCGCCGGTC?ACCGACGGCC?CGTTCGCCGA?GACCAAGGAC?CTCATCGCGG?GCTGGATGGT??8580

GATCGACGTC?GACAGCCAGG?ACCGCGCCGT?CGAGCTGGCC?GGGGAGCTGT?CGGCCGCGCC??8640

GGGGGCAGGC?GGGAAGCCGA?TCCACGAGTG?GCTGGAGCTG?CGCCCGTTCC?TCGCCGCCCC??8700

GCCCACCATC?ACCGAGTGTC?ACTGAGCGAG?ATGGACGAGG?TTCTGCTCAG?GAGCCTCACG??8760

CCGAGCGTGA?TCGGCATCCT?CGGCCGCCGC?GGAGCTGACT?TCGCGGCGGC?TGAGGACGCC??8820

GTCCAGGACG?CTCTGGTGGA?GGCCGTCCGC?GTCTGGCCTG?CCGACCCGCC?GCGCGACCCG??8880

AAGGGCTGGC?TGGTCGCTGT?CGCCTGGCGT?CGGTTCCTCG?ACGCGGCCCG?GTCCGACTCC??8940

GCCCGCCGCA?GGCGCGAGGA?CAGCGTCGAC?GGCGAGCCGG?TCCCCGGGGA?GGCGCCCGCG??9000

GTGGACGACA?CCCTCCAGCT?CTACTTCCTG?TGCGCCCACC?CGTCGCTGAC?CCCGTCGTCG??9060

GCGGTCGCGC?TCACGCTGCG?CGCCGTCGGC?GGGCTGACCA?CCCGGCAGAT?CGCCCAGGCG??9120

TATCTGGTGC?CCGAGGCGAC?CATGGCCCAG?CGCATCAGCC?GGGCCAAGCG?CACCGTCGCG??9180

GGCGTGCGCC?TGCACCAGCC?GGGGGATGTC?GCCACCGTGC?TGCGCGTGCT?CTACCTGGTC??9240

TTCAACGAGG?GCTATTCCGG?CGACGTCGAC?CTGGCCGCCG?AGGCCATCCG?GCTCACCAGG??9300

CAGCTCGCCG?CCGCGATCGA?CCACCCTGAG?GTCGCGGGCC?TGCTCGCCCT?CATGCTGCTG??9360

CACCACGCCC?GCCGCACCGC?CAGGACCGCC?CCGGACGGCA?GCCTGGTGCC?GCTCGCCGAC??9420

CAGGACCGCT?CCCGGTGGGA?CAACGCGCTG?ATCAGCGAGG?GCGTCGCGGT?CCTGCAGGCC??9480

GCCCTCTCCC?GCGAACGCCT?CGGCGAGTTC?CAGGCCCAGG?CGGCCATCGC?CGCCCTGCAC??9540

GCCGACGCCC?CGGCCGCGGG?GGAAACCGAC?TGGGTGCAGA?TCGTCGAGTG?GTACGACGAA??9600

CTCGCCCGCC?TGACCGACAA?CCCGATCGTC?CTGCTCAACC?GGGCGGTCGC?CGTCGGCGAG??9660

GCCGACGGGC?CCAGGGCGGG?CCTGGCCGCT?CTCGCCGCCC?TGGACGACGC?TCTCCCCCGC??9720

CACACCGCCG?TCGCCGCCCA?CCTGCACGAA?CGCGACGGCG?ACCGCGCGAG?AGCCGCCCGG??9780

CTCTACGCCG?AGGCCGCCAG?GAAAGCACCC?AACCTGGCCG?AACGCGACCA?CCTCACCCGC??9840

CAGGCCGCCC?GCCTCAACAC?CCGCTGACCC?CCGGCCCATC?CGCCCGGTCG?CCGTACCGTC??9900

CGGGGACGAG?TCGACAGAAG?TCGCCGACAG?AGAGCAGGAA?GCGATGCGCA?ACGAGGCAAT??9960

GGCGCGGTTG?GACGTCCTGA?CCGGATCGTG?GCGGGCGACG?CTGAGCAACG?CCTGGTTCCT?10020

GGAGCCGCCG?GACCAGGAGG?TCGAGGGCAC?GGCGACGGCC?GAATGGCTCG?CCGACGCGTT?10080

CGTGGTCTTC?CGCTGGACGA?TCAGCGGCGA?GCCAGGCACG?GCCACGACGG?AGATGGTCCT?10140

GGTCATCGGC?CGCAGCGACG?CCAACGACGC?CTACACCGCC?CTCTACCACG?ACGAGCGCGG?10200

TGTGAACCGC?GTCTTCGCCA?TGACCTTCGA?CGCCGCGCGG?TGGACGATGA?GCCGCGCGGA?10260

CCCCGACCTG?TTCCAGCGAT?TCGTCGCCGA?CGTCACGCCA?GGCCGCGTCA?CCGGCCGCTG?10320

GGAGGCGTCG?CAGGACCGCG?GCTCGACCTG?GCGCAAGGAC?TTCGACCTCG?TCTTCGAGCG?10380

GGCGTAGCGC?CTGCCCGCCC?CGGTCAGTTG?CTAGCGATCG?CCGGGTGGAT?GTCCCAGCTC?10440

GTGGCGGCCA?GGTCGGCCGG?GATAGGGCCA?GCAGGCTTGC?GCGGCGGGAC?GACGGTGGCC?10500

TGCCAGGTGT?CGGTGAGGTC?GGTCGGGGCG?CGGTCGGAGA?CCAGCATCGA?GCGGTGCAGG?10560

CGGCGCAGCG?CGGGGGACGG?CTCCAGGGCC?AGCTCGGCGA?TCATGCGGGC?GCGGACGTCG?10620

CGGTAGACCT?CCAGGGCTTC?GGAGCGCCTG?CCGGAGCGGT?AGAGGGCGAG?CATGAGGTGG?10680

GCGCAGAGGC?CCTCGTGGGT?GGGGTAGCGG?TTGACCAGGG?CGGTCAGCTC?GCCGAGCAGC?10740

TCGTAGTGCC?TGCCAAGGCG?CAGGTCGACC?TCGATGCGCC?GGTCCAGCGC?GTTGAGGTGG?10800

GCCTCCTGCA?GGCGCTTGGC?GTAGGAGTTC?AGGACGGCGC?CGGTCTGCAC?GTCCAGCAGA?10860

GGGCCGCCGC?GCCACCAGGC?GAGCGCGTCG?CTGAAGCTGC?GGGAGGCGGC?CACCAGATCG?10920

CCGGACTCCC?GCTCGCGGTG?GCCCGCGGTG?GTCAGCCGCT?CGAACGCCCA?GGCGTCCACG?10980

GACGGCTCGT?CGGCGGACAG?CACGTAGCCG?CCGGGCTGGG?TGCGCACCAG?TTCGCGGGCC?11040

ACGCTCTCGG?GTGCGTCGAC?GCGACCGGCG?AGCACCTTGG?CCGCCTGCTT?GCGCAGTTGC?11100

ATGACGTAGG?TCTGGACGAC?CGCGCGGGCG?CTGCGCGGCG?TCGTGTCCCC?CCACAGCTCG?11160

GCGATGATCG?CGTCGAGCGG?GACAACCGTG?TTCGCGTTGA?TCGCCAGCAG?CGCCAGAACC?11220

GTGCGCGGCT?TCGTCGCCGA?AGGCGCGACG?GAGACGTCAT?CGTGCGCGAC?TTCCAGCGGC?11280

CCAAGAACGC?GGATCTTCAG?CATGATCTCG?TGAATCCCCT?CTCCCCTGTC?GCCCCAGGCT?11340

CCTCCCCCCG?GAAGAACCGC?TTCCGCCGAG?TATGCCAGGC?AACTCACGAC?CGGCGTCCCC?11400

ATTGCAGGAG?TTGCCAATCC?GGAAACAGGC?GCGCCGCGCG?CCGCCACTCC?AGGGAGCGGC?11460

GGTGCGCTGG?CACTTCAGGC?AATCAGATTG?CGGAGAGCAT?CACTTCACGC?TATCGCCACC?11520

CGCCCGAGGT?AGGACTCGAT?CTCCTCAGCG?GCCTTCGCCG?CGCCACCCGC?GTGCCGGATG?11580

TGCTCGCGCA?TCTCGGCGAC?GGCGGTCCGG?ATTGCGGTGT?CGTTCGCCAC?CTGGTCCACC?11640

GCCTCCCGCA?GCCGCCCTAC?CTGCACGTCC?GCCACCTCGA?CGCGCGTGCC?GAGACCGAGG?11700

GCGACCACCC?TGGCGTGGAT?GTCGACCAGC?GGGGTCACCG?GCACGACCAC?CACCGGTGTC?11760

GCCCAGTGCA?GACCGGTCAT?CACGCTGCCG?AGTCCGCCGT?GGGTGACGAG?TGCGCTGGCG?11820

TGTTCGAGGA?CGGCCGCGTG?CGAAACCCAG?CGGTGCACCT?CGACATTCGG?CGGCAGTTCG?11880

CCCAATACGG?ACGGATCGAC?GCCATCGCCG?AGCGAGATCA?CCACATGCCA?CGCGCCATCG?11940

GCGAAATCGC?GGACGCAGGA?TCGGAAGAAA?TCGACATTCT?CGTTGTAAAC?GGTCCCGAGC?12000

GAGATAAGCA?CCACGGGCAA?TTCGGACGCA?GGCGGGCGCC?ATTCCCCAAG?GAAGTCTCGC?12060

TTGGGCAGGC?ACGGGCCGAC?GAAGACGTAG?CGCTCGCCCA?GCTTCTCCGC?GTCCTGCTGG?12120

AACGCCGACG?GCAGGAAGAC?GATGTTGAGC?GCCTCGCTGG?TGGCGGCCAG?GTACTCGGCG?12180

ACCGGCATGT?CGATGCCGTG?GCGGCCGAGC?GCGTCCTGCA?TGCGCGCGTG?CGCGGCGGCG?12240

ACCGCGCCGG?GGTCGCGCCC?CATCGGGCCC?CTGGCCTTCC?CGGTGTTGTC?CTCGGCCCAG?12300

AACTGGTCGG?TGTAGACCGG?GGTCGGGATG?GTCTGGACGA?CGGGCACGCC?CCATTCGGCC?12360

GCGATGAGCC?TGCCGATCCC?GTTCGCCATC?TGGTCGTAGA?CCACCAGATC?GGGACGCCTG?12420

TCCCCGTAGG?CCGCGCGGAC?GGCGCGCAGG?ATCGCCGCGC?CCTCGGCCAG?GAACAGCTCG?12480

AAGTTGGCCA?CCGGGTCGCC?GCCGCCGAGC?GCCCCGGTGA?GCTGCCGCCC?GACCAGCACC?12540

GACTCGTACG?GCAGCACCCG?CGCGCCGGTC?TCGGCGACGG?CGGTGGCGTA?GTCACCCGCC?12600

GCCGGGTACG?TGACGCGGTG?GCCCCTGGCC?ACCAGTTCCT?CCGCCACGCC?CAGCGTGGGC?12660

ACCACGTGGC?CGTGCGAGGC?CATGCTGACG?AACAAGATGT?CGCTCATCGG?GCGTCCGTTC?12720

GCTCGAAGGC?CCAGGTGGTG?GGCAGTTCCG?CCGGGTAGAA?GCTGAACATC?GTGCGGCCCA?12780

TGACGACCTC?GTCCGGCCGG?ACGGCGGCGC?GCAGGCCAGG?CAGGCCGCGG?ACGAGCGCGG?12840

CAAAGCCCTC?CTGCAGCTCG?ACGCGGGCCA?GCGGCGCGCC?GAGGCAGTAG?TGCCTGCCGC?12900

TGCCGAAGGA?CAGGTGCCCG?CCTGCCGCGC?CCCTGGCCAG?GTCGAACTCG?TGCGGGCGCT?12960

CGACGCGGCC?GGGGTCGCGG?CCAGCGGCGT?CGAGGGAGAT?CAGCACCTGG?GCGTGCGCCG?13020

GGATCGTCGT?GCCGCCGAGG?TCGACGTCCG?CGCTGGTGTA?GGTCATCCCG?GCGAAACCGG?13080

TGCCCGCTTG?GGCGTAGCGC?AGGACTTCCT?CGACGGCGGC?GGCGATGTCG?ACCTCGCCCG?13140

CCGCGAGCCT?GGCGAGCTGG?TCCGGGTGCT?GGAACAGGGC?CAGCAGGCCG?TTGCCGAACT?13200

GCACCGCGCC?GGTCTCGTAC?CCGGCGATGC?TGAGCAGCAC?CACGGTCGAC?ACCAATTCGG?13260

TCTCGCTGAG?CCGGTCCCCG?TCGGGCCCGC?GCACCTCGGC?CAGCGCGGGG?AGCACGCCGT?13320

CGGCGGGCTT?GCGGGCGACC?AATTCCCGCG?CGGCGTCGTG?CAGGGTGCGC?ATGGCGGCGC?13380

CGAACGCCTC?CATCGATCCG?GCCGCGCCGC?GCAGCCCGGC?CGCCCAGGCG?TCGAACGCGG?13440

GGCGCAGGTC?GGCGGGGACG?GCGTAGAGCG?CGCAGAGCAC?GTCCAGCGGT?AGCCGGAAGG?13500

CGAACTCGGC?CATGAAGTCG?ACCGGCCCGC?CCCGATCGGC?GAGCCTGCCC?ACGGCGGCAC?13560

CGGCCAGCTC?GCGCACGGCG?GGCCGGACGG?ACTCGGCGTG?GCGGGGGTTG?AGCACCTGGC?13620

CGACCAGCCG?CCGCCAGCGC?TCGTGGTCGG?CCGGGTCGGC?GATGGCGAGG?CCGAAGTCGA?13680

ACCCGCCGCC?GCCCGGCTTG?GCAGCCCGCT?CCCGGGCGGG?CCGCCTGCTG?AAGCGCTCGT?13740

CGGCCAGCAC?CGTGCGCACC?TGCTCGTGCC?CGCTGACCAG?CCAGGCGGGT?GCGCCGGTCG?13800

GCAGCCGCAC?CGGGGCGACC?GGCTCCTCGC?GGCTGAGCCG?TTCCAGCTCA?TCCGGCAGGG?13860

TGAACGGGCA?CCTGACCGGG?AACGGGTAGG?TCGCGGCGTC?GGCGCGGGTC?ATGCCGCCCG?13920

CCTGGTCATC?CGGTACCACA?TCGGTCCGGC?GTCCGGGGTG?CGGCGGACGC?TGCCGGGCAC?13980

GGCCGAGACG?AGGTCCCAGT?GCGGGGCGAA?CGCGGTGTCG?ATCTCCTCGG?GCCGCACGCT?14040

GAGCGGGCCC?TTGGTGAACG?CGTAGAGGTA?CAGCGTCGCG?CCCGGCGCGG?CCACGCCTGC?14100

GACGCCCTCG?GCGTAGCGGG?CTTTGGCCTC?GTCGCGCAGG?CTGTGCGAGC?AGCCGAAGTC?14160

GAGCAGGAAG?TCGTACGGGC?CGCCGAGCGC?GCCCGCGGGG?ATGTCGACCA?GGTCGCACTC?14220

GACGAACTCG?ACGTCGACGC?CCGCGTCCCC?GGCGCGCTTG?CGGGCGCGGC?GCAGCGCTTC?14280

CGGCGCGATG?TCGGCTCCGG?TGACCGACCA?GCCGTGCTCG?GCCAGGTAGA?TCGACTTGCC?14340

GCCGGTGCCG?CAGCCCAGGT?CCAGCGCGCG?GCCGGGGGCG?AGCCGGTCGG?GGCCCTCGAT?14400

CAGCGCGACG?AGTTCGGGCA?TAGGCGGACC?GAGGTCCCAG?GGGGAGAACC?CCACCTTGTA?14460

CGCCGCGTTG?TACACTTTGG?ACACCAACTT?GGACGACCTG?GCCGTCCTGG?ACGTCTTGGC?14520

GGTCTCGCTC?ATCGGCCGTC?TCCTCCCTGC?TTCGGCGACC?CCGCCACCAC?GTCGGCGCGC?14580

AGCGTGAACG?CCGACGCCCC?TGGCGGGTTG?AACTCCATCG?GCCTGCGCAT?CGGCTCGGCC?14640

GCCGGATCGG?TGAACGCCAG?GCCGAGCCCG?GCGAGCGCGC?CTGCGAGCGG?CCCGTCGGCC?14700

CCCGCCTCGA?CGCTGAAGTA?GCTGCGCTGG?GTCGGCGCGT?AGCCGATCAG?CTCGACCACC?14760

CTGGACACCC?CGGGCGGGCG?GCCGTAGGCG?GCCTTCTCGT?CGTCCCACAG?GTAGACCGCG?14820

CCCCAGGTCT?CGCCTTCCGG?GCCGGTGTTG?GCCACCCAGA?CCTTCTGCCG?CAGGCCGGGT?14880

GTCGCGGAGT?ACGCCTCGAC?GGCGTAGTCG?CGCAGGTAGG?AGCGCAGCGA?CGCGACGGTC?14940

TGGTCGGACT?CGGCCAGATC?CCACAGGATG?ATCGTCAGGT?GCACCGCCGT?CACCCCTTGA?15000

CGCCGACGAG?GTAGCCGGGG?TGCGCGTCGC?GGTCGTGCAC?CCTGGTCACC?GCGAGCCCGG?15060

CCCGCTCGAA?CGCCGCGCGG?TACTGCGCGT?CGGTGAACAG?GGTGTTGGTC?TCGTCCTCGT?15120

GGAACGTGCG?GATGCCGTCG?GCGTCGGCGA?CCACGAAGTG?GATGCGCATG?TGGGTCGCGC?15180

CGTCGCGCCG?CACGGAGTGG?GTGACGCGGG?AGATCACCAG?GCCGTCCTCG?CGCACCAGGT?15240

GCCCGCCGAC?GTAGCCGTCG?ATGAACTCCT?CCGGCCCCCA?CCACGGCTCG?ACGACCAGCA?15300

CTCCCCCTGG?CGACAGGTGC?GCGGCCATCC?TGGCCACGGC?GGCGTCGAGG?GCGGCGGTGT?15360

CGGGCATGTA?GGCGATGGCG?AAGCCGAGGC?AGGTGACCGC?GTCGAAGGTG?CGGCCGAGGT?15420

CGAAGGCGCG?CATGTCGCCA?GGGTGCACCT?GGCCTGCGCC?GATCCGGTCG?GCGGCGATCT?15480

CGCGCATGGC?CTCGGCAGGC?TCGACGCCCG?CGACGGCGGC?GAAGGTCTTG?GCGAAGGTCA?15540

CCAGGTGGGC?CCCGGTGCCG?CAGCCGACGT?CCAGCAGGGT?CGCCGCCGCG?GGCGCGCGGT?15600

CGCGCACCAG?CGCGGCGATC?CGCGCGGACT?CGGCGGGCCA?ATCCTTGCCC?CGGCTGCGGA?15660

ACACCAGGTC?GTAGTGCTCG?GCGTGGGCGT?GGCCGTAGGT?CATGGCGGCC?TCCTCTCTCA?15720

GGTCGTCTCA?GATGACGCGG?ACTTCGGGGA?CGTAGGTGAT?CCAGCGCCCG?CCCGCCTCGG?15780

TGAAGGCGTG?CTCCTTGGCG?AGGATTTCCT?CGGTGTGGTT?CCAGGCGAAC?AGCAGCGCGT?15840

AGTCCGGGTA?CGGCTCCGCG?AAGGCCGACG?ACGAGCGGAC?GGGGATGCCC?GAGCCGGGGG?15900

CGAGCTTGCC?GTGCTTCTCC?GGGGTGGAGT?CGCAGATGTA?GGGCACCAGT?TCCGGGGTGA?15960

TGCCGCAGTA?GTTGATGGTG?GTGGCGCTCT?TGGCCGTCGC?GCCGTACCCG?ACGACGGAGC?16020

GCCCCTCGGC?GCGCAGTCCG?CGCAGCAGCG?CGACCAGTTC?GTCGCGGGCG?TGGCGCACCC?16080

GGCCGCCGAA?CGCCTCCAGG?GTGGCCGGGT?CGGCGAGGCC?GCCCGCCTGT?TCGGCGTGCA?16140

GCCGCTCGGT?CACCGCGGCG?CTCGGCTCGG?CGCCTGCCCG?CGCGATGGTG?AACCGGATGG?16200

TGCCGCCGTG?CACCGGCAGC?CGGGTGATGT?CGACCAGCTC?GAAGCCGAAG?CGGCGGGCCA?16260

GGTTGCGCAC?CGACGTCACC?GAGAACAGGT?AGAAGTGCTC?GTCGTACACC?TGGTCGAAGG?16320

CGGTGTTCGC?CACGATGTCG?CCGAGGTAGC?GGTCTTCCAC?GACGAAGACG?CCGTCCGGGG?16380

CCAGCAGCGC?GTCCACCCCG?GCGAAGATCG?AGTCCAGGTA?GGCGATGTGG?CTGACCGTGT?16440

TGGCCGAGAA?GACGACGTCG?GCCGGACCGT?GCTCGGCGCG?CGCGGCGCGG?GCGGTGCGCT?16500

CCTCGAAGAA?GTCGACCACC?ACCGACACCC?CGGCCGCCCG?CGCGGAGTCT?GCCGCGCCGC?16560

CGGAGGGCTC?GAAGCCCAGG?TGCCGCACGC?CCGCGCCGCC?GATGGTGCGC?AGCATGACGC?16620

CGTCGTTGCA?GCCGATCTCG?ACCACGAACG?GGTCCGCTCC?GGCGAGGCGG?GTGTCGAGCA?16680

GGTGGTGGGC?GTACGCCTCG?AAGTGCTTGC?GGCTGCCGGA?AGACAGCGAG?GACCGGTAGG?16740

GGTACTCGCT?GTGGAACATC?TGCGCCCGCG?GCACTTCGGT?CAGCTGCTGC?ACCATCGCGC?16800

ATCCGCCGCA?GACGCCGATC?CTGAGGTCGT?AGTGGAACTC?CGGGGAGGTG?TCCGCCGGGT?16860

CGCGGAACGC?GTCGGACACC?GGCTGTCGGC?CGAAGTCGAA?GAACTCGCGG?ACCGGTCCGC?16920

TGCAGAGTCG?ACATGCGCCC?ATGCCGGTGA?GGCTACGGTC?GTGCTGCGTC?ATCGTCGTGG?16980

CTCCTAGAGG?GGCGTTATAG?CGGCATTCGA?CCGGTGCTGT?GCGCGGTCGC?GTGCCTCGTC?17040

GAGAAGTTCC?AGCGCGCGCA?CGCTCACGGC?CAGTTCTCCT?GCGAGGTGGT?CAGCGGATCG?17100

GGTGCCGCCG?CGCACGGCCG?AGGCGAACTC?GGCCATCACG?GCGGCGAACT?GGTCGAACGG?17160

CGCGATCCCG?ACGCGCCGCG?ACCCGCCGGG?GCGCTCGAGC?ACCACCTCGG?TGGCCGCCGA?17220

CGGCGGCGGC?GTGTACGCCC?GCGCCGCGGT?GACGGCCCCC?GCGGTCCCGC?ACAGCTCGTA?17280

GGCGGCGCGG?TAGTGGTGGT?CGATGCCGAA?GGTCAGGTGC?GCGACCGCGC?CCCGAGCCGT?17340

GCTCAGCAGC?AGCGCGCCGC?CGAGGTCGAC?GCCCAGGCGC?TCGTCCCGCT?CCACCACGGC?17400

GCCGTCCAGG?CGCACGTCAT?GACCGAGCAG?CAGAAGCGCG?GTGTGCAGCG?GGTAGTAGCC?17460

GACGTCGAGC?AGTGCTCCGC?CGCCGAGGTC?GGCGCGGTAG?CGAATGTCGT?CGGCGGGGCG?17520

CGGCGGGATC?GTCATGCCAG?CCGAGAGCAC?CCTGGGCAGG?CCGATCTCGC?CGCGCGCCAC?17580

CGCGTCGCGC?ACGACCCGGT?GCTGCGGGTG?CCTGGTGAAC?ATCCGGTTCT?CCATCAGCAC?17640

CAGCCCGGCC?CGCTCGGCGC?GCTCGGCGAG?CGCGGCGGCG?TCGGCGGCGG?TGGCCGCCAT?17700

CGGCTTCTCC?ACCAGCACGT?GCTTGCCCGC?CGCCAGCGCC?TCGGCGGCCC?ACTCGGCGTG?17760

CAGGCCGGTG?GGCACCGCGA?TGTAGACGGC?CTCGACGGCA?TCGTCGGCGA?GCAGCGCGCG?17820

GTAGCCGTGC?ACCGCGGCGC?AGCCGAACTC?CGCGCCGAAC?GCGGCGGCCT?TGGCCGCGCT?17880

GCGGCTGGCG?ACGGCGACCG?TCACCGTGCT?CGCGCAGGCG?GCCAGCGCGG?GCAGCGCGCG?17940

GCGGCGGGCG?ATGTCGGCGC?AGCCCAGCAC?CCCGACCCGC?AGCGGCCTCA?CCCGTCCGCC?18000

CTGCCGGGCA?GGCAGGCCAG?CAGGCTGCGG?GCCTGGATGT?TCAGGTAGTG?GCTGTGCCGC?18060

ACCAGGTCCG?CGGCCTGGTG?CAGGGCGACC?CACTTGAACC?CGGCGCGCTC?CAGGTCCCCG?18120

GTCGGGCCGG?TGTCGGCCGC?GCTGTCCTCC?ACGACCAGGT?AGCGGGTGCG?GGCGTGGTAG?18180

AACCGGCCGC?CCTCCTCGGA?CATGGTGGCG?TCGAACAGGA?CCCGCTCGGC?GGGCGCGGAG?18240

AGGACGGCGT?CCAGGAAGCG?GGGCCGGGCC?TCGGCGGGCA?GGAAGCCGTA?GTTCGCGGGG?18300

GTGCACTGCA?CGGTCGGCGC?CAGCTCGGCG?ACGTCGAGGC?AGCCTGGTTC?GGGGCGGACC?18360

TGGAGCAGCG?CGTGCTGGAC?GCCGCCGATG?CGGCGCACCA?GGAACGCGAC?CAGGCCGACG?18420

TCGCGCACGG?CGAGCATGGG?CTGCGTCCAC?TCGGCGACCT?CCCGGCCGCA?CGCGCGCACC?18480

GACACCCCGA?CGACCTCGAA?GAACAGCCCG?CTGTCGTGGC?GGATCGCGCC?GTCGGCCTGG?18540

GACCAGCCCG?TGAGTCCGCG?CAGCGGCGAC?CTGCGCACGT?CGATCTCCGC?CGCGGTGCGC?18600

GCGGAGGTGA?TCCAGCTCAA?CAGCTCCCGC?GTCGGGTGCA?GGCTGCCGTC?GTCCGCCTCG?18660

CCGGGGAGCG?GCAGCGGCAA?ACAGGACAGC?ACGGTGCGGG?CGTCCATGTT?GATCAGGTCG?18720

TCCTCGGCGA?GGAGGCGGCG?GACGGTGGCC?AGGGTGAGCC?AGCAGAAGCC?GTCCCTGGCC?18780

GCTGTCGAAC?CGTCCGCTCC?GCCGCTGTCC?ACCTCGCTGC?TGTCCAACTC?GCTGCTGTCC?18840

AACTCGCTGC?TGTCCAACTC?GATGACCATG?TTGCGGTTGC?GCTTGCGCAG?GAACCACGCG?18900

CCCTGCTCGG?ACTGGCGCAC?GTCGGCGATG?ACGCGGGCCG?GGTCCGGCTC?CAGGAAGTGC?18960

TCCAGGTACG?GCACCGCGGC?GCCGCCGTGC?ACCCTGGTGT?AGTTGCTGCG?GGTGGCCTGC?19020

ACGGTCGGCG?AGAGCTGGAC?GCCGTTGCAG?TTGCCCGGCT?CGGCCTTGGC?CTGCATGAGC?19080

AGGTGCAGGA?CGCCGTCGAA?CTCGGCGACG?GCGATGCCCA?GCACACCGAC?CTCGGGCTGG?19140

TTGATGATCG?GCTGGCTCCA?GCCGGGCACC?GGTCCGGCCG?GGTCGCGCAC?GTCGATGCCG?19200

TGCACGGTGA?AGAACTTGCC?GCTGCGGTGG?CCGATGTCGC?CGGTCTCCGG?ATCGGCAGCC?19260

CAGCCGCGCA?GGTCGGCCAG?CGGGACGCGC?TCGACGTGCA?TCCACGCCCG?CTCGCGCTGC?19320

TCGGCCAGCC?AGGCGTGCAC?GTCCGGCGGC?TCGACGGCGG?TCGGCCCGGA?CGCGGCGGAC?19380

TCGGCGAGGC?GGGCGCCGAT?CGCGCCCCTG?GCGAGCATCC?CGGTCATCGC?GCCACCCCCG?19440

CGGTGCGGGC?GGCGAGCGCC?GCCTTGAGCC?CGTCGACCAC?CGCGGTGACG?TCGGCGTCGG?19500

AAAGGCCCTG?GTGCATCGGC?AGGCAGAGCG?TGCGCTCCGC?GGCGTGGTCC?GCCCCGGGGA?19560

GCTCGGCCGT?GGAGCCGAAC?GCGGCGACCC?GGTGCAGCGA?CGGGTAGCGG?TAGGTCGTGT?19620

AGATGCCGCG?CTGGTAGAGG?TCGCGGGCGA?CCTCGTCGCG?CAGGTGCGGC?GGCAGCTGGA?19680

CCCAGTAGAA?GTAGTGCGAG?CCGCGGTGTC?CGGCCGGCAG?CGGCGGCGGG?ATGTCGACCA?19740

GGTCGGCGAA?CTCGCGGTCG?TAGTGCGCCG?ACACCTCGGC?GCGCCGGGTC?AGGAACTCGC?19800

CCAGTCTGCC?CAGCTGCACG?CAGCCGATGG?CGGCCAGCAC?GTCGTTCATC?ACCGAGCGGC?19860

GGGAGAACGA?GGAGACCTCG?AAGTCCCACC?AGCGCGTCGC?GGCCCGCTCG?GCCTGGGCGA?19920

AGCCGCTGGT?CTGCTCCAGG?CCGAGGTAGG?CGAGCTTGCG?CCCGCGCTCG?ATGTGCTCTG?19980

GGTCGCGGGC?GTGCAGCATG?CCGCCGTCGA?CCGAGACGGC?GATCTTGCCG?TGGTCGAAGC?20040

TCCACACGCC?GAAGTCGCCG?AAGGTTCCGC?AGGCGCGGTC?GCCGATGGCG?GAGGCGGGCG?20100

CGTTGGCCGC?GTCCTCGATG?AGCAGCAGCC?CGCGCTCGGT?GCACAGCGCG?GCAATCCGGT?20160

CGACCTGGCC?GGGGTGGCCG?CCGTAGTGCA?GCACCACCAC?CGCCTTGGTG?GCCGGGGTGA?20220

GCGCCGCCTC?GACGTGCTCG?GCGGTCGGGT?TGAGCGTGCG?CGGGTCGACG?TCGCAGAACA?20280

CCGGGCGCGC?GCCGTGCGCG?GCCACCGCGT?TGGCGGCGCT?GACGAAGCAG?ACGGTGGGCA?20340

GCACGACGTC?GTCGCCCGGC?CCGACCCCGG?CCAGGCGCAT?CGCCAGGAAC?GTGGCCTCGG?20400

TGCAGGTGTC?GGCGGACATC?AGGTGCCCTC?CGCCGACACC?GAGGTGCGCG?GCGAAGCGGG?20460

CCTCGAACTC?GGCGACCCGA?GGACCCTTGC?CCACCCAGTT?GGACGCGAAG?ACCTCGCCCA?20520

CGGCGGCCAG?TTCCTCCGCG?CCCAGCGACG?GCTGGAACAC?ATTGATCATC?TCGGGCCTCC?20580

CCCAGGATCG?TCAGCGGTAG?TGCAGGGCGG?TGATGGACTG?CGCGAACCCG?TCGTCGGCGC?20640

GCTGGAGCGC?GCCGAGGTCG?AGGTCCGGTC?GCGCGGCGAG?CAGCCCGCGC?AGCGCGGCGA?20700

CCACCTGCGC?GCGGGCGCTG?GCCGCGCCGA?GGCAGTAGTG?CGCGCCCTTG?CCGAAGGTGA?20760

TGTTCTCCGC?GCGCGAGCGG?CCGGGGCAGA?ACGCGGCCGG?GTCGGCCACC?TTCGCCGGGT?20820

CGGCGTTGAC?CGCCGGGATG?TCGACCACGA?TCGCCGTGCG?CGGCTCCAGC?CGGACACCGA?20880

GGCAGTCGCA?CGGCTCGGTG?ACCCAGCCGA?AGATCCCGAG?GAACGGCGGC?GCGAGCCGCA?20940

TCGCCTCCTC?CGCCACCCCG?GCGAGGTCCG?CCCCGACCGC?CTCCGGCCGG?GTCAGCAGCG?21000

CGTGCGCCGC?CACCGCGATC?CCGGTCTCCA?CCTGCGGCAC?GCCCGCGGCG?AGCAGCTGCC?21060

CGACGGTGGC?CACGTCCGCC?CACGGGATCT?CGCCGTCGGC?CTCGGCCTGC?GCCAGGAACG?21120

CGGCGGCCAG?CGGGGTCGGG?TCGGGCGCGG?CCAGCGCCTC?GGCGGTGGCG?TCGCGCAGGA?21180

ACGCCAGCAC?CGAGCCGAAC?GCGGCGCGCT?GGCGCTGCGG?CAGGTCGAGC?ACGCCGAGGA?21240

AGCGCTGCTT?GATCACGAAC?ATCAGCACCC?GGTACGACTT?CGCCAGGTTG?GCCTGGTGCC?21300

GCGCCGGGAA?GCCCATGAAC?CGGAAGGTGC?TGTCCAGGGC?GAACGGCGCG?ATGAAGTCCG?21360

CCACCAGGTC?GCCTTCGGCG?GGCAGCGCCT?CGGCCAGCTC?CCTGGCCCTG?GCCTCGAACG?21420

CGGGGGCGAA?CGCCGCCACC?GCTGCGGCGC?TGTAGGCCGC?GCGCAGGCGG?TGCTTGAACG?21480

TCGGGTGGTT?GGCCCCGCGC?CGGTACCACA?GCTCGAAGAA?CTGCGACACC?GTCGGCACGT?21540

CGTCCGCGCC?CGGCGTCGGC?ACGGCCGCCC?GGTCGGGGTC?GAGCGCGGTG?CCGATGTGCG?21600

GGTCGCGCAG?CACGGTGTCG?GCCACCTCGT?GGGTGGTGAC?CACCCACTGG?TTGGTCTCGG?21660

CCCGCCAGAG?CAGGCCGTGC?GGCGGCGCCT?GGGTGTCAGC?CATCGCTCCT?CGCCGGGGTC?21720

AGGTGGACGG?GCAGGGCGGT?GTAGCCGCGC?GTCATGAACT?CCGGGAAGCG?GACGGCGCCG?21780

GACGACGGCG?TCACCGCGTC?CGCCGCGTCG?ACGAGCGCGG?CCAGCATGTG?CGACATGGCC?21840

TGCCGCGACA?TCGCCGCGCC?CAGGCAGGAC?GTCGCGCCCC?AGCCGAACGT?CAGGTGCCGG?21900

GCCGCGGCGC?GGGTGTCCCG?GCCGACGTCG?AAGGTGTCCG?CGTCCGGCCA?CTGCGCCGGG?21960

TCGCGGTTGG?CCGAGCCGAC?CAGGCACAGC?ACCAGCCCGC?CCGCCGGGAT?CGGCGTGCCG?22020

TCGATGACCA?CATCGGCGCG?GGCGAGCCTG?CCCAGCGCCT?GCGTGGACGG?GTCGTAGCGC?22080

AGCCCTTCCT?CGACCGCGCC?GGGAACCAGC?GCGCGGTCGG?CGCGCACCCT?GGCGTACTGA?22140

CCCGGGTGCC?TGGCGAGCGC?GTCGACCAGC?GTGCCGAAGC?TGAGCACCAG?GCCCTGGTGG?22200

GTGACCAGGG?AGATCATCAG?CCCGGTGCCG?AGCACGAACT?CCAGGTGCTC?CCCGACGCCG?22260

CCGCCCCCGG?TGAGCGTGCC?CGGGTTGGCG?ACCAGGTGGC?CGATGAAGTC?CTGGGTGGGC?22320

TCGCGGAGCC?TGCCGACGGC?GCTGCGGGCC?AGCAGCTCGC?GGATGCCGCG?CACGATCCGG?22380

CGCTGGTCGG?CCGCATCGGC?AGGCGGGCCG?TACCCGCTTT?CCGCCCACGC?CCGGAACGCG?22440

GGCAGGTCGG?CGTCGGCGAT?GGCCATCAGG?TCGGCGAGCA?GCCGGGTAGC?CAGCGGGATG?22500

GCGTAGTCGG?CGACGACGTC?CACCGGGCCT?GGCCGGGCGG?CGAGGTCGGC?GGCCAGCTCC?22560

CGGCAGGCGG?CGGCGAAGCC?CGGCCACAGC?CCGTCGACGT?AGCCGGTGGA?CAGCGCCCGC?22620

CCGGTGGTGC?GCCTGCCCTG?GGCCCGGTGC?GCGGACGCGT?CGGGCTCCGG?CGGCGGCTCC?22680

GGCAGGGCGT?AGGAGCGCGC?GCCGGAGACC?ACCGCGGCTT?GCAGGCCGCG?CAGCATCGGC?22740

TGGCCCACCG?CGGAGAACCG?GCTGTCGCCG?AACACCGCGT?GGCACTGGGC?GTGGGTGGCG?22800

GCGAACCAGC?AGTCCCACAC?CGACGAGCGC?ACCGGGGCGC?CCGCGCCGCG?CAGCCGCGCG?22860

TAGTGCGGGT?ACGGGTTCTC?GACGAGCGCG?GCGTCGGCGA?GGTCGACCGG?CTCGACGGGG?22920

ATCGTGGTGG?TCATGGCGGT?TGCCTCGGCG?TCCTCTCAGG?AGTCCAGCTG?GACCGGGGTG?22980

TCGTCGGCGA?GCACGCTCTT?CTTCAGCTCC?GACCAGGTGC?GCGCCCGGTC?GGCGACGGTC?23040

GTCAGCACGA?CGACGTAGCC?GTCCGGGTCG?GTGGCCTCCA?CGTCGACGGT?GTTCCACGGG?23100

GTGGCGAGCG?GGCCGTTGAC?GGTGCCCTGC?GGCAGCGCCC?CGGCGCGCGC?GGCGATCTCC?23160

CGCATCGACG?CCTCGGTCTC?GGCGTTGAGC?GTGAAGCTGA?TCCGCACGCC?CCTGCCGAGC?23220

GGACCGTCCA?GCGGCTCGCG?GGCCGGGCGC?AGCAGCATGT?CCCGGTACTG?GGCGCGGCGC?23280

AGGTGGATGA?CGGCGATCTG?CCCGTCCGGG?CCGGTGAGCT?TCTTCTCGAT?CCAGAAGCCG?23340

AGGCCGTCGA?CGTACCACTG?CAGCGACTTC?TCCAGGTCGG?AGACGAGCAG?CACGGCGAAG?23400

TTCGGCATGT?CGGGGATGTC?GTCGAAGCCG?ACGCCCTCGG?GTGCGGCCTC?GTGGCTGGGG?23460

TGGTTGGCGT?GGGTGGTCAC?GGCGGTTCCC?TTTCCCGGGT?GGGTCGTCAG?CTGTAGGGCA?23520

GTGCCCGGAC?TTCTTTGAGG?TTGTTGTGGG?TGTCGATGCG?CACGGCGGCC?GGATCGATGC?23580

GCAGGCCCGG?CCGGGCGGTG?ACCAAGGCGC?GCAGCGCGGC?GGCGACCTGG?CGGCGAGCGG?23640

TGTTGGCGCC?CAGGCAGTAG?TGCCCGCCCC?GGCCGAAGGT?CAGCACCGCG?GTTGGCCGCA?23700

CCGGGCAGCC?GCGCACGGGC?GCGGTCGGCC?CGCTCTCGGC?CAGGTTGACG?GCCTCGGTGT?23760

CGATCGCCAC?GATCGTGCCC?GGCTCCAGCG?GCACGCCCAG?GCACGAGCAC?GGCTCCGCGA?23820

CGAACCGGAA?CACGTTGCCG?AACGGCGGGC?TCTGCCGCAT?GCACTCCTCG?GCGACCTCGC?23880

CTGCGTCGAC?CTCGCCTGCG?CGCAGCAGGC?CGGGCAGTTC?CGGGTCGGAC?CAGACCATCC?23940

GGCTGGCGAT?GGCCCCGCCG?ACGATCATCG?GCTCGATCCC?GGCCATGAGC?AGCTGCCCGA?24000

TGAGCGCGGC?GATCGGCCAG?GTGCTGCGGT?CCATCGCCGA?GAGCCTGCGG?GCGGCGTCGA?24060

CGAACGGGGA?GTCGGCTTCG?GCCAGCAGCC?GGTCGGTGAG?GTCCTTGAGG?TAGCGCATGA?24120

CCGCGGCGAA?CGCGGCCTGC?TCGCGCGCGC?CGTAGTCGGT?GACGCCGAGG?AGCTGCTGCT?24180

TGAACAGGTG?GATGACCAGC?TTGGCGACCT?TGGTCAGGTT?CGGCCAGTCC?GCCTCCGGCA?24240

CGCCGATCAT?GGCGAAGGTG?CTGTCCATGA?AGAACGGCGA?GAAGTAGTCG?CGCGCCAGGT?24300

CGCCGTCGGC?GGGCAGCGCG?GCGGCGCGCT?CGGCGGCCAT?CCGCTCGAAC?ATGTCCACAT?24360

AGGAGTCCGC?GGAGCGGATG?GTGAACACCT?TGCGCAGCTC?GGTGTTGAAC?GGCGCGTAGT?24420

TGTCCGAGAC?CGTGTACCAC?AGCTCGAAGA?ACTGGGTGAT?GCTCGGCGTC?GCGTTCTCCT?24480

CCGGCATGGC?CGTGGCCATG?CCTGCGCGGC?TGCGGTCGAC?CCCGGTGATG?ATGTGCGGGT?24540

CGCGCAGCAC?GACGTCGGCC?AGCGCCGGGC?TGAGCACCTT?GAGCCGGTTG?CGGCCCGCGT?24600

CCCAGCGCAG?CCCGTCGGGC?AGCGCGGTGG?CGGCGAGTGC?GACGCTCATG?CGATCACCGG?24660

GAGTTCCCTG?GGGTAGTAGG?TGAACAGGTT?GCTCGCCAGC?GGGACCGCGT?CGAGGTCGCC?24720

GTCGTAGCGC?AGGTTCGGGA?ACCGGGTCAG?CAGGCGCAGG?ATGCCCTCCT?GCATCTCCGC?24780

GCGGGCCAGC?GCCGCGCCGA?GGCAGAAGTG?CGGGCCGCTG?CCGAAGGCGA?GCTGGCGGGC?24840

CGGGGCGACC?CTGGTGACGT?CGAACTTCTC?GGCGTCGGGG?CCGAACACCT?CCTGGTCGCG?24900

GTTGCCGGAG?CCGAGCGAGA?CGAACACGGT?GCCGCCCGCC?GGGATGGTGG?CGCCCGGCAT?24960

CGGGATGTCC?TCGGTGGCGA?ACTTGGCCAC?CGCGAAGCCG?GTGCCCATCT?GCGCCCAGCG?25020

CAGGATCTCC?TCCACCGCGC?CGCCGATCAG?CTCGGGCCGC?TCGCGCAGCA?GCGCCAGCTG?25080

CTCGGGGTGG?CGGAACAGCG?CGTAGAACGC?GTTGCCGAAC?TGCACGGCGG?TGCTCTCGTA?25140

GCCCGCCATC?AGCAGCAGGA?TGACCGTGGA?CACCAGCTCC?TCGTTGGACA?GCTGGGTCTC?25200

GTCGTCGTCG?CGGAGCTGGA?TGAGCGTGCT?CAGCAGGTCG?TCGCCGAGGT?TCTTGCGCTT?25260

GCGGACGATG?AGCCCGACGG?CGTAGCGGCC?GATGCCCTGC?AGCGCCTCGC?CGAACGCGGC?25320

GAACCCGGAC?TGCATGTCGC?GGCGGGTCAG?CTTGGCGGCC?AGCTCGGTGA?ACTCCGGCCT?25380

GCTCTCGTTC?GGGATGCCCA?GCAGGTCGCA?GATGATCCGG?ATGGGCAGCT?TGTAGGCGTA?25440

GTCCGCCATC?AGGTCGAACG?ACGGCCCGCG?CGCTTCCAGC?TCGTCGAGCA?CCTCCTCGGT?25500

GTGCCTGGCG?ATCTCGGCGC?GCATCGCGTC?GGCCTGCCGC?TGGGTGAACG?CCTTGTTGAC?25560

GATGCGCCGC?CAGCGGGTGT?GGCCGGGCGG?CTGGGAGATC?GAGCCGCCGA?AGGTGAACAC?25620

CGGGCTGGAG?CGGTCGGCGG?AGAACCCGGT?GTCGACGCGG?GCCGCGCCCT?CGCGGTTGAT?25680

GGTGCGGCTG?AAGCGGTCGT?CGCCGAGCGC?GGCCTTGACG?TCGCCGTACT?TGGTGATCAG?25740

CCAGGCCAGG?TCCCCGCTCT?GCAGCTTCAC?CTGCGCCACC?GGCTCGTTCT?CCCGCGCCCA?25800

GGCGAACTCC?TCGGGCATGG?CGAACGGGCA?CTTGCGCTCG?AACGGGTAGG?TCTTGCCGGT?25860

CAGGCCCACT?GTGCTGTCCT?GGCTGTCTTG?GCCGTCCTGG?CTGTCCTGGC?CGTCCTGGGT?25920

GGTCACTGTG?TTGTCCTGGG?TGCTCACTGC?GGTCTCCCCT?GTGGTGGTCA?TGGCGTGCCG?25980

ATCAGCTGCG?CGCGGTGCGA?GCGGACGCGG?GATTCCAGGC?CCGCGTCGAC?GGGCGTGCCA?26040

GCGCACCCGC?TCAGCACGTG?GTGGCCCAGG?TACCCCAGGA?ACGCCTCCAG?CTCCGGGATG?26100

AGGCCAAAGC?GGTTGTTGTG?CGTGTGCAGG?TAGGACACGA?GCAGCACCTG?CGCGCGCCGG?26160

GCCGCGGACG?CGTCATCGCC?CGCCAGCCTC?ACCCGGTCCA?GCACCGCGGG?ACCGGCCTCG?26220

TGCACCCTGG?CCCACGCGCG?GCCCACGGCG?TCGTGCATCG?GGTCGCCCGC?GAGCGCGCCC?26280

CGGTTGGCCA?GGACGGCCTC?GGTGTGCGCG?CGCAGCGGAG?CCGAGTGCTC?GGCGAGCAGG?26340

GCAGGCCAGG?CGTCGAGGAA?GCCGTCGAAG?ACGTACGGCG?ACCAGATCAC?GCAGTAGTGG?26400

GCGAAGAACG?CGGCCATCTC?GGCGGGCGTC?AGGTCGGTGG?CGCACAGGCC?GCGCAGCATC?26460

ATGCCGTAGC?CCATGCCGGT?GCGCTTGCTC?GACTTGCCGC?CGACCGCGCG?CAGCGCGTCG?26520

ACCACGATGG?CGCTGCTGTC?GCCGAAGTAG?TCCTCGGCGA?CAGCCACGCC?GTCCGGCCCG?26580

CCGTACTTGT?CGTGCTCGGG?GGCGTACTCG?ACGCGGCGGA?CGCTGTCCGG?CGGGTGGATC?26640

TCCTCGGCGG?CGGTGCCCTC?CAGCGCCGCC?ATCGTCGGCT?GCGCCTCGCG?GTGGAACTCC?26700

TCGGCGTCGA?ACTGCTCGGC?CGCCGGGTGC?TCGGCCAGGT?AGGCGCGCAG?CTTGCCATCG?26760

ACCTCCCCGA?CGACCGCGTC?GGCGTCGGTC?TCGGCGACCC?GCATCCGCAC?CCGGATGTGG?26820

TGCCCGCCCT?GCCAGTAGCG?CAGGAAGAAC?CACCCGTGGA?TCGCGCCGGA?CTCGCGCAGC?26880

AGCTCCAGCA?CGGGCGCTAT?CCCGTCGGTG?ATCAGGGTGT?CCTGGTCGGC?GTAGCGGTGC?26940

ACGTGCAGCG?CCCGCCACAC?GGGTTCACCG?GGCATCGCAA?CCTCCGGTAA?GGGTGTGCTC?27000

GACGAAGAAC?TCCTCGGCGC?TCCCGGCGCC?GGAGGCGTAG?CCCTCAGCTC?CGGGGAGGCA?27060

TTCCTGCACG?ACGACGTGAC?CGCCGGGGGT?GGCGCGGGCC?TGCTTGGCCA?GCACGTGCAG?27120

CAGGAACGGG?TTGGCCGCGT?CGAGGTAGTG?CGGCTTGTGC?AGCCGGGCGC?TGCGCGCCTG?27180

CAGCGCCCAC?TCGCGGGTCT?CGGCGGCGTA?GTCGCGCTCG?CCGTCGGCGC?GCACCGGCGG?27240

GGCGACGACC?CGGAAGAACG?CGTGCCGGGG?CAGCCCGGCC?GCGCGCCGCC?ACGCGTCGAA?27300

CTCGGCCAGC?GCGGTCAGCT?CCTGGCGCTC?CAGCCCGTCC?AGCGCGGGCA?GGTCGGCCAC?27360

CGGCAGCCGC?CACGAGCGGC?GGTCCAGCAC?CAGCCCGCCG?AGCCGCACCC?TCGGCCGGTC?27420

GGCCGGGGCG?AGCCCGGCGC?GGTCGAGCTG?GTCCCACAGC?CCGCCCCGGT?AGGTGCGGGT?27480

GGGCGCGAAC?GCGCAGAGGA?ACCGGTAGAG?CATCGGCGCG?GCGGCCGGGT?ACAGGAAGTT?27540

CAGCGGGGCC?AGGTCGATCC?GCTCACCGTC?CTGTGTGGAC?CACAGGGCCA?GGCGGCGGGT?27600

GGTCGGGTCG?GCGCGGACGA?CGAGGTCGGC?CAGGGTCAGC?ACGCCGGTCG?CGCCGGGGCG?27660

CTGCACCGAG?CCGGGGTAGA?CGACCTCCAG?CGGGGTCAGC?CTCGGGTGCA?GGTTGAAGTT?27720

CAGGCCGAGC?GCGGCGGTGA?TGTCGGCCTG?CCTCGGCGTG?TGCCTGGCGA?TCGTGTCGCG?27780

CAGCGACCCG?GCCAGGTCGA?ACCGACCGCC?ACCCAGCAGA?TCGCAGTAGC?GGGAAAAGAA?27840

GACTCCGTGC?CCGGTGGTGA?TGCCGTTGAC?CACGGTGAGG?TCGTCGGCCT?GCTGCACCCG?27900

GTAGGCGGTG?GAGCGCCACG?GCACGACCGT?CGGCGGCAGC?GCGTCGACCA?CCGAGGCCAG?27960

ATGCGCCGGG?TCGAGCACCA?GTTCGCCGTC?GGCGCGCTGG?TCGCGGACCC?AGCCGAGGAA?28020

GTCGCGGCGC?AGGGCCAGCA?CGTGCTGGGC?GTGCGGGTCG?CCGACACCGC?ACATCACCGC?28080

GCTCGCCTCG?GCGGGCGAGA?GCGCGGAGAA?CGCCTCGTAC?AGCTCCACGA?CAGGAACACC?28140

CGCGTGGTCC?TCGCCGAAGC?GGTCGGCGAA?GAACGCGTAC?AGGCCCAGCT?TCTCCACGAT?28200

GGCGTCGTCC?AGCAGCGGCA?CCAGGCGCTG?GAGCAGGTCC?AGGTTCTCCC?GGTCGCGCTC?28260

CAGCAGCGCG?GGCCGCCAGC?TGTCGGCGTG?CGCGCGGGTG?CCGACGTCCT?CGTACAGCGC?28320

GGCGCGCATG?GCCTCGCGGG?CGGGCGGCGG?GCAGCCGACG?ACCTCCACGA?ACCGGGCCAC?28380

CAGCGCGCGC?AGCTCGGCCA?GCAGCCCGGT?GCGCCGCGCG?GCGGGCGCGT?CGGCGAAGGC?28440

GTCCTCGACG?GCTTGCAGGC?CGGTGAACAC?CTCGGCGCAG?GCCAGCGCCT?GCGCGGTGCC?28500

CACGGCCGCC?AGCCTGCTGG?CGACCTCCTC?GGCGACCCGG?TCGGCCTGGT?CGGGCAGGCC?28560

GAGGCCGCGG?TGGCACAGCC?CGGCGCGGAC?GAGCTGGTCG?ATGGTGCCAG?CCGCGGCGTC?28620

GGCGGCCAGC?CCGGCGTCGA?CGAGCCGGGC?GCGCAGGTCG?TCCTCGGTGC?GGTCGTGGTC?28680

GGCGAGCAGA?CCGACGAGCA?CCCGCACCAG?CGGCGAGTTC?TTGGCCCGGA?TCACCTGGTC?28740

GGGCCGGAAC?CCGTCGTCGG?CGCCCTCCAG?CGGCCTGCGC?ACGGAGACGG?CGTGCTCGCC?28800

GCGCACGGCG?AGGGAGTTGT?TGAGCCGCAC?CCGCAGCAGC?GCACCCGCGC?CGTCGACCCG?28860

GTGCAGCTGG?TGGGTCATCC?AGGCGAGCAG?GCCGACGCTG?AGCCGCGCCC?GCGCGACCCG?28920

CTCCCCCGCC?GCGGGCGCCG?CCCCCCAGGG?CTGGGCCCCG?ATCTCGGTGA?ACGCGCCGAA?28980

CGGCGAGGGC?TTGAAGACGA?CGCGGTAGGC?GAAGCTGGTG?ATCGTGCTCT?CCGCCCTGCG?29040

CCGCTTGGCA?GGCTTGCGGG?TGGTGTCGAA?CGGGTCGCCC?GCGTACGCGG?TGACCTCCCG?29100

GTGCACGTCC?TCGCCGGAGA?GCTGCACGCC?GCGCTGGAAG?TCCTCGCCGA?GGGCGACGGC?29160

GGCCAGCGCC?TTGCGCGCGC?TCTCCAGCTC?GGCGGCGTAG?ACCTCCTCGG?CCAGCGCCTC?29220

CAGCTCCGCG?CCGCGCCTGC?GCGCCGCGAC?CCACTCGCCG?ACCCGCTCGG?CGAGGTCGCC?29280

GGGCAGCGGC?GGAACCGACG?CGGGAACGCG?GTCGTTGTGC?ACGTCGCGGC?GCAGCTTCAG?29340

CACGGCCCTG?CGCTCGGCGT?CGGCCACCTC?GGGGACGACG?GCGTGCAGGG?CGTCGGACAG?29400

GCGGGCGCGC?AGCGGCTCGC?GGACGGCGCG?CTCGGCGTCG?GCGGCGGCCA?GCAGCTCCCA?29460

GGTGCGCGTC?GGCACCAGGC?CCGCCAGCGC?GGGCAGGCCG?ATGGTGCCGC?GCCGGAACAG?29520

CACGTGCGGA?CTGAACTCCC?CGCTCATCGC?GGCATCACCG?CGACCTCCCA?GTGGGTGCTC?29580

GGACGGACGG?CGCCCACGCA?CACCTGCGCG?TGGACCCCTC?GGTCGGCTGG?CAGGGCGTAG?29640

GCCAGGTCGA?TCGGGCCGAC?GTCGAAGCCC?AGGACGGCGT?GGCCGCTGAG?CCGCGCCGCG?29700

GTGGCGGCCA?GGCACACCGC?CTCCACCACC?GCGCCGACGC?CGAGCTGGCG?GGCGCGGTAT?29760

CCCGCGGCGC?CGCCCGCGAA?GTCGACGGGG?CCGGTGACGT?GGACGGTGAA?CGCGGCCAGC?29820

TCCGGGTTGA?GCGACTCGGC?GAACAGCGCG?CGCCGCAGCA?CCGGGCCGGG?GTCGTCCTCG?29880

GCGACCGGGA?CGAGCGCGCC?GTCGAAGCGG?TACCAGCCGG?GGGCCAGCCC?CTCGACGCGG?29940

CGCACGGCGC?AGCACAGCCC?GGCCTCCGCG?CCGACCGCGC?CGCCGGAGAC?CGCCGCCAGC?30000

CGGGCCGCCG?CCTCTGCCGC?GTGCAGCAGG?ACGGCCTCGA?CGTCGGCCAG?CCGCACCGGG?30060

GCTCCGGTGA?ACCGGCGGCC?GTGCGAGCCC?CGGCGCACCA?TGACGCCGGG?GTCCAGCAGG?30120

TCCAGCGGTC?CGCGCACGGC?GGCGGGCCGG?TCGACGGCCA?CCGGCTCGGC?GGGCTGGCGG?30180

GCGGCCTCGG?TCAGCGCGCT?CAGGCCGGGC?AGCCGCCGGA?CAGCGCGCGA?GCGCTCCAGC?30240

ACCGGGGGCG?GCGCGGCGCG?CTCGGCGGGC?GGCTCGGCCG?GGCAGTCCCG?CCGACGCCCC?30300

AGCTCGACCG?CCGCGAACAC?GGCCTCGTCG?CGCCCGTCGA?GGCCGAGCAG?GTCCTCGACC?30360

GCCGCGGCGT?CCAGGTCGAC?CAGGACGGCG?ATGTCGCCGA?AGGCCGCCTC?GGCGACGCGG?30420

GCCGCCCGGC?CCAGCGCGAC?CCCGGTGTCC?ACCGCGCCGA?GCCGGGCGGC?GAACTCGCCG?30480

TACTTGTAGG?CGTTCTTCCA?GAACCGGTTG?GCCACCAGCA?GCACGGCCGG?GGGCAGCGGG?30540

GCGTCGGCGG?GCTCGCCGAG?CGCGGCCCGC?AGCGCGGCGC?GGGGCGCGGG?GCGGCCCAGG?30600

TCGACCAGCT?CGTGCCGGTA?CGGGTCGTAG?TGGCTGACCC?GGCCCGCTTC?GGTGTCCACG?30660

ACGTACGCCT?CGGTCGGGTA?CATCGACCCG?CCGGACGGGA?TCGGCCTGCG?CGGGGCGTAG?30720

CGCTCCCCCA?GGTGCGTCGG?CGTCGGGTTG?TCCGGTGTGG?ACGGCATGCC?GCCCGCCGGG?30780

TCGAACCGGA?CGGCGGTCAT?GCCGAAGGTG?AACAGCAGCA?GCCGGTCCAG?CGCGCCCGCG?30840

CGGCCAAGCG?GGGTGCGTAC?GCCGCCCGCG?TAGACCTTGA?CCGGCCACGG?TCCGTCGGCC?30900

CAGTCGACGC?GCCAGCCGTC?GGGGTTGGCG?CCCTGCGGGT?CGCGGCGCAG?CGACTCGGTG?30960

TGCTCGGCGA?GGTCGCCGGT?CACGGGAACG?GGTGCGGCAC?GCATCCCGGC?TCCTCCCCGT?31020

CGACCAGTCC?GGACCGGTAG?GGCAGTCCCG?CGCCGCCCGC?CAGGCGGGGC?AGGTCGCGGG?31080

TGCGCCGGTT?GCGGTGGCCG?AACGTCATCG?GGACCGCGCC?GGGCACGACG?ACCCGCACGC?31140

AGGTCAGGCC?GTTGCGGCGC?AGTTCTGGCA?TGGTCTGGTC?GACCACGAGC?ACGTCCATGC?31200

CCGCGGCCAG?CACGCCGGAC?ACGGCGACGT?CGAGGTCGGC?GCGCAGGTCG?GGCTCGCGCT?31260

CGCGCAGCGT?GCCGGGCACG?TCGGCCAGGG?CGACCCGCCC?CGCATCCGCG?TCCAGCAGGA?31320

ACGACCAGCG?CTCGCGGGCC?TCGGGCAGCG?CGCCGACCAG?GGAGTGGTCT?TCCATCCTGG?31380

TCATCAGCGC?CGGGTCGGCG?AGCATGGCCA?GCCCGTCGGC?GCGCCTGCGC?TCGTAGGAGT?31440

GCCGGGTGGC?GAGCACGCTG?CCGATCAGCT?CGTGCAGACC?GCCCGCGATG?GCCTGCACCG?31500

GGTCCGGGTG?CGCCCCGGCT?CCGGCGAAGA?CGCGCGGCCC?GTCGTCGAGC?CTGCTCTCCG?31560

CGACGAGCCA?GGTACACGGC?ATTCGATACT?CCATAGTGGA?CAGGAAAGCC?CGGAAGCGGA?31620

AGCCGGTGAA?CAGCTCCGCC?TTGCGCAGCA?GCGCGTCCAG?CCCGGCGTCC?GCGCCCACCA?31680

TGTCGATCTC?GGGCAGGGCG?AGCCTGCGGT?ACCAGGCCAT?CAGGAACGAG?TCGCGCTCGG?31740

CGACCTCGCG?CAGCCCGTGC?AGCACGGCCT?CCTCCGCGGA?GTTGCCGAGC?GCGCAGCCGT?31800

TGGAGGTGTC?GTAGAGGAAC?GCGGTCTCAC?CGTCGTGGCG?GGGGCCCCAG?AACGCGGCCC?31860

GCTCCGGCAG?CAGCACCCGC?TCGCCGCGGC?GCATCGAGTA?CGCCCACACC?CAGTCCACGA?31920

CGGTGTCCCG?GTCGAACCGG?CGGAAACGGA?AGCCCGGCTC?GGCGTAGGAC?GCCTCGGGGT?31980

GGGTGCCCAG?CGTCGTCGGG?TCGATCGCCC?GGTCGGCGAC?GTCGGCGTAG?CAGGCCCGCA?32040

CCGGGGCGCT?CCGGCCGCCG?CGGTGCAGCC?CGGCGTAGCG?CTCCAGGCCC?TCCAGGACGG?32100

CGATGGTGCG?GCTGCTGCGG?TAGGTGCGGC?CCCGGCCGAT?GGCGGGCTCG?CGCCTGCCCC?32160

ACCGGGTGCC?CAGTTCCACC?GAGCAGGCGC?CGATTGGGCT?CTGCAGGTCC?TGGCGGACCT?32220

CCTTGAACAG?CCCGATCCCG?GCGAACAGGT?AGTCCTTGGC?GACGGTGTCG?GCGTCCAGTT?32280

CGGCGGTGCG?CAGCGAGCGC?GGGCCGAGCT?TGGGCAGCGG?CACCTCCCTC?GGGGTGAACA?32340

CCGGCACGGT?GTCCGCCTCG?GCCCCGCCGC?AGCTCGCGCA?GGTGGAGTCG?GGCAGCAGCA?32400

CCTGCCGGTC?GACGGTCGCC?GTCACGCCGT?CGACCACGGT?CACCTCGCAG?TCCGGGCTGC?32460

CAGGGCCGTC?CGGACCGCTG?TCGGCCATCC?GCTCGCGCAC?CAGCCGCTCG?ACGGCGGCCA?32520

GCACGCCCGG?CCCGAGGGTG?AACGTGGCGG?TGTCGCGCCG?CGAGGACTCC?GGGGCGGTGT?32580

CGCCGCGCAG?GTCCGGGCCG?AACGGCGAGT?TCGCCGTGCG?GGTGACCAGG?CAGTGCGGGC?32640

ACCCCGGCAC?CCGGCTCGCC?CACAGCGGTC?CGATGTAGAC?CAGCGAGCGG?TAGGTGCCGA?32700

CGAACAGCAG?CGGCCTGCCA?GTGCCCAAGC?ACTCCACGAT?CAGGTCGTGG?TGCTCGCCGA?32760

TGCGGTCCAG?CTCGGCGACC?AGCACGGTGT?CGACGCCCGC?GGGCGGGTCG?GCGGAGAGCC?32820

GCCTGCCCAG?CTCGTCGGCG?AGGAAGCCGG?TGCCCGCGAC?CTGCGGGGCC?GCCACGTGGG?32880

TGATCACCGG?AGCCGAGAGG?GTCACCGGGC?ACCTCCCGGG?ATGGCGGCGA?GGCACGCGGC?32940

GTCGCCGAGG?AACGGCAGCA?GGTGGGTCAC?GTCGGCTGGC?TCGGGCGGGC?GGCCCTGGGC?33000

GCGGACCGCG?GCGACCGCCT?CCGGCCAGGT?GGCGACCGGT?GGGGCCAGGT?GGGCGACGGC?33060

GTCGCCGCGC?CCGGCGACGG?CGCGCAGCAG?CGCGTTGCCG?ACGGCGTGCG?CTGCGTCGAT?33120

GCCGACGCCC?TCGGCGACCT?CGAAGTCCGC?GGTGCGCACC?CGCGCCCGGT?GCAGGCCGGT?33180

GGGCAGCGCC?TCCAGCGCGG?TCGCCGTCCA?CGGGCGTCCC?TCGGCGGCGA?GGGTGTCGGT?33240

GAGGAAGCCG?TGCACGGGGT?CAGCCCCGTG?CGGCTCGGCG?GACTGCCAGC?TCAGCGACGC?33300

AGGCGGCAGG?GCGAGCGAGG?CCGCGGCGAC?CGCCCGGTAC?CACGCCTCCG?CCGACGTCCA?33360

GCCCGCTCCC?CAGGCCGCGT?CCGCCGGGCC?GACGCCGTGG?TCGGCGAGCC?TGCCAGCGGT?33420

CCACTCCAGC?GCGGCCAGCA?CGACCTGGTT?GCGCGCTTCC?CGCGGCGACA?CCGCGCGGCA?33480

GACGAGCAGC?CTGCTGGCGC?GCTCCACCGG?GTCGGCGATC?AGGCAGGTGC?TGGCCGAGAG?33540

CGGGAGCTGG?TCTGCCTCGC?CTTCGCCGAG?GGAGAGCAGC?GGGCCGACCA?CCTGGTCGGT?33600

CCAGCCCGCG?GTGGCGCCGA?CGATCCGGTC?GGACACCGCG?GTCAGCCGCG?GCGGGTCCTG?33660

CGGGGCCGGG?ACGTCCGGGC?GCACCGGCTC?GACCCGCTCG?ACCACCGCGG?CCGTCGCCGC?33720

GCCGTGGCGC?CTGCACATCG?GGTGCCGCCT?GCCGGTGTGC?GTGCGCACCA?CCGGGGCCAG?33780

CGGCTCGGCC?GAGGTGAGCA?GCCCGGCGCC?GTCGAGGTCG?ACCTCGGCGA?GGCGGGCGAA?33840

GACGTGCTGG?GCGACGTGCA?GCGCGGCCAG?CGCGGCCGGG?GTCGCCGCCG?GGGCCAGCCC?33900

GGTGGCCCCG?CCGACGGGGG?CCGCGACGAC?CGAGCGGTGC?ACGCACTCCC?AGCACCAGTC?33960

CACTCCGGAC?GGCGGCGCGG?CGGCCACCAG?GTAGCCGGAG?ACCGTGGCGA?GCACGGCGAC?34020

CGGGCTGCCG?GTGGCGCGCA?GCCGCCACTG?CAGGTCGGCG?AGGGCGGCCG?GGTCGGCGTC?34080

GTCGACGGCC?AGCACGACCT?CGTCGGTGTC?GGGGAACTCG?GCGAACGCCG?CCAGGTCGGC?34140

GTGGTCGAGG?GTCCAGGCCA?GGTGCGGGTC?GCGCTCGGCC?GCCTCGGCGA?CCACGACGGC?34200

GGCCTCGGGA?TCGGTGGAGA?CGATCCTGGC?GGTGGCGATG?CCGAACTCGG?CCAGCGCGTC?34260

CAGCGCGGCG?CGCAGCGCCA?CCCCGGAGCC?GCCGACGAGC?ACCGGGCGGG?TCCGCACCCT?34320

GGTCATCCTG?GTGACCGGCC?GGTCGGCGTG?GTGGTCGAGG?AACGCCAGGT?GGGCCGGGTA?34380

GCGCTCGCGC?ATCCAGTCGG?GGGCGTGCTC?GACCGGGTGC?TCCACGCGCT?TGAGGAAGCC?34440

GTTGCCCGCC?AGCGTGTCGA?TCAGCCGGGC?GACGGAGCGG?CTCGGGCCGT?CGGGCAGCCC?34500

GGCGCACAGG?TCGGCGACGC?TGCGCTCGCC?GTCGAGGTGG?GCGAACACGG?TCTCCACCAG?34560

TTCGTAGGCG?CCCTTGCCCC?GGATGGAGAA?GGAGCCGTGG?TCGTTGCGCA?GCCAGACGCC?34620

GTCGTCGTGG?CGGACGAAGA?ACGCGTCGGC?CTTGACGGCG?AAGCAGCGGG?TGTCGGCGCT?34680

CATGACAGCT?TCCCGTTCGG?GCTGTAGGCG?GCCAGGGCCA?GTTCCTCCGG?CACGCATTCG?34740

ACGCGGCTGG?GCCGCTCGGC?CTCCGGCAGC?GCGGCGCAGT?GCTCGCGGAC?GTCGTCGGCC?34800

GACGCCGAGC?CGACGACGCG?GGCCACGAGG?TGCTCAAGGC?CGGTGTCGGC?GCGGTGGATG?34860

GCGACCTTGG?CGTCGGCGAC?GCCGGGCAGC?GCGAGCAGGT?GGCGCTCGAC?GGCCCTCGGG?34920

TAGACGAGGA?CGCCGTGCAG?CTTCTCGCCG?CCGTCCACGC?GGCCTTCCAG?GCAGAGCCTG?34980

CCCTCGGCGT?CGAAGCGCCC?GTAGTCGGTG?GAGGCGACGT?AGCCGCCGTT?GCGGCGCAGC?35040

GCCTCCCCCG?GCCGCCAGGT?GCCCAGGCAG?CAGTCCGGGC?CCGCGACGGC?GACCGCGCCG?35100

ATCCCGTCGG?GGTCGGTCCC?CTCCAGCCAG?ACGGCTTTGC?CCGCGACCGG?GACGCCGACG?35160

TGCTGGTTGT?GGCCGGGGTC?CTGGTCGACG?GCGACGGCGC?CGGTCTCGGC?GGTGCCGTAG?35220

AGGTTGCGCA?CCGACACCCC?GGAGAAGCGC?TCCCGCACCA?TCCGGACGCG?CTCGGCGCCC?35280

AAGTGCCCGC?CGCCGAGGAA?CAGCGTTATG?CGGCTCGCGT?CGACCTGGCG?GTCCATCGTC?35340

AGGCACGCCG?CGGCGGCGAG?CGCGGGGACC?GCCAGCACGG?CGATGTCGCG?CTCGGCGGCC?35400

TCGGCGTGCG?CGGCCGACCA?GTCGTGCGCC?GGGAAGACCA?GCAGGTCGCG?GCGCAGGAAC?35460

AGGCTCGGGA?GCACGGTCAT?GAAGAAGGAA?GCGGAGAACT?GCAGCGGAAG?GCAGGTGGCC?35520

AGCACCGGCG?GCATGCCGTC?GGCGGAGCAG?TCGCCGTAGA?GGGAGCGCTC?GTAGTGCAGC?35580

GCGATGGACT?CCCAGGAGTC?GGCGTGGCCG?ATGGCCAGCT?TCGCGTTGCC?GGTGCTGCCC?35640

GAGGTCGCCA?CACCCCACAA?CGGGCGCTCC?AGCGGCCCGT?CGACCGGCAG?GTCGGCCTCG?35700

GCCAGGCCGG?GGGCCAGCTC?GCGCCCGCCC?GGCCCGGAAG?ACCACAGCAG?CACCGTGTCC?35760

GCCACGGTGG?CCACCGCGAA?CAGCGAGACC?AGCGACTCCA?GCCCGGCTGC?CGGGTCGACC?35820

CGGTAGGCCC?GCTGCGGGGC?GACCAGCGCG?GAGCGCTCGC?GGCCCCGGTC?GAGCAGTTCG?35880

TCCCAGGTCG?CGCTCTCCCC?GCCCCAGCGC?ACGCCAGTGT?CCGCGCGCCG?GGCTAGGAAA?35940

CGAGTGAACG?CCGCAGCGCC?CATGCCACCC?ACCCTTCGAT?CGTCGACGGC?CTGTCCCCGG?36000

CGGGTTCCCG?CTGCGCGAGG?CCCTTGCGGG?TCAGGTAGGA?CAGCGCGGTC?ACCGACTCCA?36060

GCGAGTCCAG?CGGCCGGGCC?GGGTCGTTCT?CGCGCAGCAG?CGCGCGCAGC?GCCGCGCCGA?36120

GCCAGAACTC?CTCGACGGCG?GCGGTGAACG?CCTCGGGCGC?GTCGTGCGAG?GCGATGTGGC?36180

CCGCGCCGTC?GAGGAGCACC?CCGTGCACGC?GGGGGCCGTA?GGAGCGCGCC?GCCAGCGCGG?36240

CCTCGCGCTC?CGCGGACTTG?AGCGTGCCGT?TGACCAGCAG?CACGTCGCAG?CCGAGCGCGC?36300

CGAGCCGCTC?GGCAGCGATC?CTGGCGCGGT?CGTCGAACTC?CGCCGTGGCG?TGCCCGCTGA?36360

ACTCCGCGAG?CGTGGTGCGC?CAGCGGCCGG?GGTGCAGCCG?GTCGTACTCG?GCGGCGAGTT?36420

CGGGGTTCTC?CTCGACCAGG?ACCCCGAACC?CGTCGAGCAG?CCGCGCGAAC?GACTCCCGGT?36480

CGGCTCCGGG?GAAGAAGCCG?GTCAGCACCA?GCGACTCCAC?CAGCTCCGGC?CGCGCCTCGG?36540

CGAGCCGCAC?GGCCAGCGGT?CCGCCGAGGT?GGGAGGCCGC?GACCAGGTGG?CCGGGGCCGA?36600

AGTGGTCCAC?CAGGGCCGCG?ACGTACTCCA?GTGCGGTGTC?CAGGTAGTCC?GGCCCGGCGT?36660

CGACCGGGCA?CCGGCCGTGG?CCGGGCAGGT?CGACCGGCAC?CACCCGGCGC?CGCCCCGACC?36720

ACGCGGCGAT?CTGCGCGCCG?AAGTGGCCGT?AGGCGGTGCC?GAGCAGGCCG?TGCAGGAAGT?36780

ACACCGGGGA?ACTGCCGTCC?CCGGCCGCCT?CGCGCGACAT?CGTGATTCCT?CCGGGAGTCG?36840

TCCTGCCTCA?GCCGATCGGG?ATGACGGCCG?CGCCCACCGA?CGGGTTGGCG?AAGTGGCCGA?36900

CCTTGGTGCC?GCCCGCCTCG?ATGCGGCCCA?GGATGTGCCG?GGGCCTGCGC?AGGTCGGCGA?36960

CCAGGAACTG?CGAGGTCGTC?TCCTCGTTGC?GGGCCTGCGA?GTCGGCGCGG?TAGGGCGCCA?37020

CGTCCGGGCT?GCCCGGGCTG?ATGACGCCCG?CCAGGCCGAT?CGCCTGGTCC?TGGAACTCCT?37080

GCGGCTCGCG?GGTGGTCAGC?ACCAGGCGCT?GCTCGGGGCA?GGTGAAGGCG?AGCACGGCCA?37140

TGAGCCGCAT?GTACTCGTCG?TCCTTGATCC?GGGTGCTGTC?CCGCGAGCTC?ATGGCCGGGC?37200

GCATGCGCGG?CACCGACAGG?TCCACGACGG?CGTCGCGGTC?CTTCAGGTGC?GCCCCGTGCG?37260

CGACCAGGGT?GACCAGCTCG?GCGGCCACAT?CCAGGTGCAG?TCCGATGAGG?ACACCGGGGT?37320

TGACGTAGCG?GAACCCCTTG?TCGAGCCAGC?GGTCGAAGGA?CACGACGCGG?CGGTCGTAGT?37380

CGGCCTTGGG?CACGCCGCTG?ACCGTGTCGC?CCATGAACTT?GCTGTAGGAG?TCGCGGTCGT?37440

AGGTCTCCTG?GAACACGCAC?ATGGTGACCG?GGTCGTCGCG?GCGGACCCAC?TCGGCGAGCA?37500

CGTCGATCTC?GTCGGGCTCC?ATGCTGCCGA?TGTTGAAGTA?GACCCGCTCG?AAGCCCATGT?37560

CCAGCGCGGT?GCGGATCGCC?CAGCCGATGC?GGAAGGCGGT?CGAGAGCCGG?GTGTACTTGT?37620

CCTCGTACTC?GCCGGTGAGG?AAGCCGACGC?CGCGCACGCC?CTCGTGCTCG?AACAGGATGC?37680

GCAGCTGGTC?GATGATCTCG?TCGCGGCCGG?AGAACTTGCG?CTCCATGCGG?GCGTTGCCCT?37740

TGCGCATCGA?GCACATCTTG?CACTCGGAGT?CGCAGTGGTT?GGTCGTGTAG?AGCGGGACGA?37800

ACGTGTGCAG?CCGGGGCGTG?CGCTCCGCGC?AGCGCAGCTC?CGCGGCGGCG?ACCAGCTCCG?37860

CGGTGCTCAC?CGACTCGTCC?TCCCAGAGCG?CCAGCGCGAC?CGCGGGCCGG?GACGCGCCCG?37920

GCTCGTCGTC?CGGGCCCAGC?GCGAGCACCG?CACGGGTGTC?GACGGTCGCC?GCCTCGATGC?37980

GCACCTGAGC?CAGATCCGGC?AGCACGAAGT?CGGGATGACC?GGTACCGGGG?TATTCCGCCA?38040

TGACTAGTTC?CTTCCCGCGT?TGCGCGGCAG?ATCCGCACAA?ATGGGTTCGC?TGCTTGATTC?38100

GACTATCGGG?GCCAGATATC?GCCGAACCGG?CCGCGCCAGT?GGCCCAGCAC?GTTCGAGGTA?38160

ACACGACCCC?GGCAGGCCGT?GTCATGGGGA?AGTTCCTGCA?ACTAGGCCGC?TGACCAGGGA?38220

ATTTACTTGT?GCCAGTAGCT?CAGATTCATG?GCGCGTGAGC?CGAATCGATG?GCGATCGTAG?38280

AGCGGTTATA?TAGCGTTCTT?TCGTCGCCAC?CGAGAATCTT?GGCCGCAAGT?TCGGAGACTG?38340

CTTGACACCC?CGGTCGCCGG?ATCAATAACT?TCGGTGTCGG?GGCCAGGCGA?ATCCGGTACG?38400

AACCACAAGC?CCATAAGAAA?GAGGTGTTTC?CATGTCCGCT?GACCTGTCTG?CGCTGAACAT?38460

CGACTCCCTG?GAGATCTCGG?AGTTCCTGGA?CGACAGCCGC?CTGGAGGACA?GCGAGGTCGT?38520

GGCCAAGGTC?ATGTCGGCCT?CCTGCACCAC?CTGCGAGTGC?TCCTGCAGCT?GCTCGTCCTG?38580

ATCAGCCCGA?GGGGTTTCCC?CCCTCGCGTG?CGGTGACGTG?CGGTCCCGCG?ACCTTCCCGG?38640

CCCAGCCTGG?CCACCGGAGG?GTTGCGGGAC?CGCCGCCCGC?GGTCAGGCGC?GGACCACGAG?38700

AAAGGACCGA?CCCATGTCGA?CCGCCGTGTC?TCTATCGTCC?CTTGTGGACG?TGGTGCCCGC?38760

GCCAGCGCCG?AACCTGCCGT?CCTCGACCGA?CGAGCAGCAC?ATGCTGATGC?TCTACGTGCA?38820

CGTCCCGTTC?TGCCACTCCA?AGTGCACCTT?CTGCGACTGG?GTGCAGGCGA?TCCCGACCAA?38880

GGACCTGCTG?CGCAAGCCCG?AGGACTCGGT?CCGCAAGAAC?TACATCCGCG?CCCTGGTCAC?38940

CGAGATCGAG?ACCCGGGGCG?CGCAGCTTCG?GGCCGCTGGC?CAGGTGCCCT?ACGTCGTCTA?39000

CTGGGGCGGC?GGCACCGCGT?CCAGCCTGGA?CAACGCCGAG?GCCGAGGCGA?TCTGGGGCGC?39060

GCTGGACTCC?GCGTTCGACC?TCAGCACCGT?CGCCGAGGCG?ACCATCGAGT?GCAGCCCCGA?39120

CACCGTCGAC?AAGGCCAAGC?TGGAGTTCTT?CCGCGGCCTG?GGCTTCAACC?GCGTCTCCAG?39180

CGGCGTGCAG?TCCTTCGACG?ACGCGCGCCT?GCGCAGGCTC?GGCAGGCGCC?ACACCGCGGG?39240

CGAGGCCGAC?CGCATCGTGC?ACCACGCCCG?CGAGGCGGGC?TTCGACGAGG?TGTCCATCGA?39300

CATCATGTCC?GGCTTCCCCG?ACCAGGAGCT?GGACGAGCTG?CGCGCGACCG?TCGAGAAGGC?39360

GGTGTCGCTG?CCGCTGACCC?ACCTGTCGCT?GTACTCCTTC?CGCCCGACGC?CGGGCACGTT?39420

CATGCGCCGC?AAGCTCGCGG?GCACCGAGAA?GCGCGCGTAC?CTGCGCAAGC?AGCAGGCCCT?39480

GTTCACCGAG?GCCCGCCGCA?TGATCATCGA?CGCCGGCCTG?CCCGAGTACG?CCTCCGGCTA?39540

CTTCGGCAGG?GTGTCGCCGT?TCGCGGCCAT?GTACTTCCAG?CTGCGCGCCG?ACACCGCGGG?39600

CTTCGGCTCC?GGCGCGATCT?CCCTGGTCGA?CCGCCAGTTC?CTCTCCCACG?CCAAGGGCAA?39660

GCTGCACGCC?TACATCCAGG?ACCCGCTGGC?CTACGACATC?GATGTGCCCG?CAGGCCAAGA?39720

CCGCGTGCTG?GTCTCGTTCC?TGCAGGCAGG?CCTCGCCATG?TTCGACGGCG?TCCTGCGCGA?39780

GGAGTGGCGC?GTCTCCACCG?GCACCGACCT?CGACGAGGTG?CTCACCCGCC?CGTCGATCGC?39840

CCCGCTCGCG?GACTTCCTGC?GCGGGCGCGG?CCTGATCGAG?GACGAGCGCG?GCATCCGCCT?39900

CGACCCCCGG?CTGGCCGGGC?TGACCCTGAT?CGAGCTGGCC?TTCGAGATGG?CCATGTCCCA?39960

GCCGGAGTCG?GCGTGACCTG?GACGGAACTG?GTCTTCCCGG?CGACCCAGGA?CGAGCAGCCC?40020

GGCCTGGTCG?CCGGGGTGCT?CGCCCCGCTG?CTGGCCGACC?TCGACCGCCC?CGGCCTGTTC?40080

CTGCGCGAAC?TCGGCCCCGA?GGGCGCCACC?CGACTGCTGC?TCCAAGTCCG?CGACGCCCCA?40140

CCGGACCTGC?CGACCAGGAC?CGCGGCCCTG?CCCGTGCAGC?CGACGGCCGT?GCGCGCTGCC?40200

ACCGTCGCCC?CGCTGGGCGG?CCCGGTCTTC?GACGGCCCCG?GCCTGGACGA?GACCACCCGC?40260

GGCTTCCTGG?CGGACACCGC?GCCGGTGGCC?GTCGACCTGT?CCACCCGCCC?CGACCGCACC?40320

GGCGCGGCCC?TGACCCTGAT?GACCGCCCAC?CTCGCCGCGG?TGGCCGACCC?GGCCCGCTCC?40380

GGCGACGGCC?CTCCGCTGAG?CTTCCTCAGC?TTCCGCTCCC?ACGCCGAGGC?GTTCCTGGCC?40440

ACCACCCGCG?ACCCGAACGC?CGCCCGGCAC?GCCTTCGACA?CCCGCTACAC?CGACCACCGC?40500

ACCACCGTCG?AAGCCGCCGT?CCGGGCGATC?CTGCTCGACG?GCGACCCTGG?CGACGCCGCG?40560

CCCTGGTCCG?CCGCGGCCCG?CGCCGCGAAA?CCCCGGTTCA?CCGCGGGCTT?CGCCAGCGCG?40620

GACCTGGTCG?CCCACACCGG?CTACACCCGC?GACCACCTCC?GGGAACGCAC?GGACTTCGCG?40680

GACAACCCGT?TCCACAGCAG?GGCGGGCGCG?TCCGAGCAGC?TACAGGCGTA?CCTGGGCGGC?40740

GACCCGTCAT?TCCTGGCGAC?CCGCCTGCTC?ACCAGCCTGC?TCTACGTGAC?CCTGCACTCG?40800

TCGGGGGTCA?GCCTGATGCA?GCGCTACTTC?CTCTGCCACG?CCATAGCCAA?GGCCTGCGAG?40860

TCGATCTACC?ACGTCGACAG?CATGAGCCTG?CTGGCAGACC?TGGCGGTCGG?GTAGCCCGGA?40920

CTCCCGCGGT?GCCGCTCCCG?TCAGCGGGGG?CGGCGCCGCG?GTGTCGGATC?ATCCGTCGCG?40980

CATCACCGGC?CGCTTGCTGC?TCAGCGCAAG?GTCGTGAGCA?GGTCTCGGCA?GGCCCGCTCG?41040

CAGCGGCGGC?ACGCCTCGGC?GCACGTGCGG?CAGTGCTCGT?GGTGGTCGGC?GTGCTCGGCG?41100

CACTGGTCCC?CGCACCGCTT?GCAGGCCAGG?GCGCACGTTT?CCAGCAGGGC?TCGAATCACG?41160

TCCTGGTCGG?GGGCGGTGCG?TCGGGAGAGC?ACGCGGCCGG?TCGTCTCGCA?CACGTCGGCG?41220

CAGTCGAGGT?CGCTGCGCAC?GCAGTCGACC?AACTCGGCGA?CCGACGGCTC?GCCGAGACAG?41280

GCGTCGGCGC?ACGCGGTACA?CGTCTGGGCA?CACTCGAAGC?ACGCCTCGAT?GCACGCCGCC?41340

AGTTCGGCGG?TGCCGGTCTC?GTTCGAGGCG?TGCGGGTGGG?ACTCCAACAT?CTGGGTTGCG?41400

ACACCCATCG?GCCTTGCTCC?CTCCGTGATT?CGTCGACCGC?GCAGCCTGCG?CTCCCCATGG?41460

CTACCCGACG?ATCGCCGCAG?GAAACGTGCG?CTCACCGGCC?ACCGCCGGTC?GCGGCGACCG?41520

GGCGCTCGGC?CGACCGCGGG?AGGGGGCACA?GGTCACGCAA?GCCCGCTGGC?AGGTAGGCGA?41580

CCAGCCGCCG?GTCGAGGTCG?GTGGAGCGCG?GGTGCGGCGG?CTCGATGCGG?AGGGGAAGTC?41640

CGCGGACCGC?GTCGGCCAGG?AAGCGGGCGA?CCGCGTTCGG?GGGCGGGAGG?AGGTCGGGGC?41700

CGAGGTAGCC?GAGGACGGTC?AGGGCCGGGT?GGCTTTCGGT?GGCGACGGAC?CAGCCGTGCC?41760

GCTCGCTCCA?GAGGAGGGCG?GCGTCGCGGC?CCGCTATGCG?CTGGTCCACC?GCGAGGTAGA?41820

CCGACACCGG?AGGACCGAGG?TCGACCGCGC?TCGCGGCCGG?TCCCGCCCCG?ACGGCGTCGC?41880

CCACGGCGGC?GACGTACTCG?CCGAGGTTGC?GTTCCACTGC?CGGGTCGTTG?ACGTCGAGCG?41940

TCGAAGTGAT?CATGTCGTGG?CCGTGCCTGG?TCGGTTCGGT?GGGGACAGGC?AGAGCAGGGG?42000

GTGGGCGTCG?GGCGCCCACC?CCCGCGGGGC?TCAGGCGTCG?ATCTGCTTGG?GCTCGGCCGG?42060

GTCCGCGCCT?GCGACGGAGA?TCTTGCGGGG?CTTGGCCCGT?TCGGCCACCG?GGATGCGGAG?42120

GGTGAGGACG?CCGTTCTCGT?ACGCGGCCTG?GATGCGGTCG?GTGTCCAGAC?CGTCGCCGAG?42180

GAACAGCTGG?CGGGAGAAGA?CGCCGTGCGG?GCGCTCGGCG?ATCTGCGTCT?CGGCGCCCTC?42240

GCCCACGGCG?GTGGGCCTGC?GCTCGGCCTT?GACGGTGAGG?ACGTTGCGCT?CGATGTCGAG?42300

GTCGATGGCC?TCCGAGGTCA?CGCCGGGCAG?GTCGAAGACG?ACGACGAACT?CGTCGCCCTG?42360

CCGGTAGGCG?TCCATCGGCA?TCGCCGCTGG?ACGGGTCCAT?GTGCCGAACA?CCTGCTGGGT?42420

CAGTCGATCC?AGCTCCCGGA?ACGGGTCGGT?GCGCATCAAC?ATGTCCGGTC?ACCTCCTGGT?42480

TGTCGTAGGG?GTGTCAATGC?AGCACGACTC?CGTTGTAGCA?TGTCGTCGAA?ACGATGACAA?42540

CTGTGATGTC?AACCAGAGGA?CGACATGGAG?TATCAGGAAG?CCCGCGACGA?CCTGAGCCCG?42600

CGCTACGGGG?ACGTCCCCTC?CATGCAACTC?GTCGAGGACG?TCGCCCGGGG?CGAGGCTGAC?42660

CCGGCGCACG?TGCTGTCGGC?CCTGGTCCTG?GTCCGGCACC?TGCGCGCGCA?CCTCGGCGAA?42720

CTGGAGCCGC?AGCTGATCGC?CGCCGCGCGC?GAGCGGGGCG?TCAGCTGGGC?CCGCCTGGCC?42780

CCCGCGCTCG?GCGTGGCGAG?CCGCCAGGCC?GCCGAGCGCC?GCTACCTGCG?CCTGCGCCCC?42840

GACGACGACC?ACGCCACCGG?CGAGGAGCGC?GTCCGCGCCG?AACGCGACCG?GCGGGCGGGC?42900

GACCGGGCCG?TCACCGCGTG?GGCGGCCCGC?AACTCCGCCG?CGCTGCGCGG?ACTCGCGGGC?42960

CAGGTCGCGG?GCCTGCCCCA?CCTGACCGGC?GACGCCCGCC?GCACCGCCGA?CGACGTCCAC?43020

ACGGCGCTGG?GCGGCGACCG?GGCGAGCGAC?CTCCTGGCCC?CCCTGCACGA?CGCCGCCCCG?43080

CACCTGCGCG?CCGCCCACCC?CGGCCTCGCC?GACCGCATCG?ACGCCGTCAC?CGCCGAGACC?43140

ACCCGCCTGC?GCCACGCCTC?CCGCGACCGC?TGACGGGCCG?CGCGGCCCAG?CCCTGCGTGA?43200

GGTCCGCCGT?AACGGGTAAG?CACCTGCATG?TTCTTCGATT?CGTGGACCGG?TCTCGTGCGG?43260

GTCGTCCTGG?TCGGCCTTCC?CGCGTACGCG?ACCCTGGTGC?TGGCGCTGCG?TCTGTCCGGC?43320

AAGCGAACCC?TGGCCAAGAT?GAACGCCTTC?GACCTGGTGG?TCACCGTGGC?CCTGGGCTCC?43380

ACCCTGGCGA?CCATCCTCCT?GACCTCGAAC?GTCGCCCTGG?CTGAGGGCAT?CTTCGCCATG?43440

GCGGTGCTGG?TGGCCGCCCA?GTTCGCCGTC?GCATGGGCGG?CCGTCCGCTC?CCCCCGCATC?43500

CGCCGAGCCG?TGAAATCCAC?CCCGACGCTG?CTGGCCCGCC?ACGGCCGACT?GGACGAGGAC?43560

GCCATGCGGG?AACAGCGCGT?GACCAGGTCG?GAGATACTCC?AGGCCGTCCG?GTCCGCGGGC?43620

TCCGGCGGCC?TTGACCAGGT?AGCCGCGGTC?GTGCTGGAAA?CCGACGGCAG?CCTCAGCGTC?43680

ATCACCACCG?GCAAAGCGGG?GGACTCCACA?GCCCTGTCCG?ACGTGACGGA?CGTGCCACGA?43740

CACGACACCC?GCGGCTGACC?CGCCGCGAGG?CAGGGCACTT?GGACGGCGCC?CAACCCCACA?43800

GCATTCATTG?ACGTTCATCG?ATGAAGCGTT?GTACCGTTCC?ATCGATCACC?CTCGATCAAA?43860

GGGAGCGGGC?TATGCGGGAT?CAGGACAGTG?CACTGCGCGA?CGAGGTCCGC?GGTCGGTACG?43920

CGGCGGCGGC?GACAGCGGTG?GCCCAGGGTG?GGGGCGGATG?TTGCGGCCCA?GAGCTGATCG?43980

ACGTGGACAG?TTCCTTCGGC?GTCGGTCTGT?ACGGGGAGCA?GGACCGGGAC?GGACTGCCCG?44040

CCCAGGCGCT?CGCCGCCTCG?CTGGGCTGCG?GGAACCCGAC?CGCGGTCGCC?GAGTTGCGCG?44100

CCGGTGAGCG?GGTGCTGGAC?CTGGGCTCCG?GCGGCGGGAT?CGACGTGCTG?CTGTCGGCGC?44160

GGCGGGTCGG?GCCGACCGGC?AAGGCGTACG?GCGTGGACAT?GACCGACGAG?ATGCTGGCCC?44220

TGGCCCTGGC?GAATAAGGCG?AGCGCGGGCG?CGGACAACGT?CGAGTTCCTC?AAGGGCACCA?44280

TCGAGGCGCT?GCCGCTGCCC?GCTGGCACGA?TCGACGTGGT?GATCTCCAAC?TGCGTGATCA?44340

ACCTGTCGGT?GGACAAGCCC?GCGGTGTTCG?CCGAGATGTT?CCGGGTGCTC?GCCCCCGGCG?44400

GCCGGATCGG?CGTGTCGGAC?GTGGTGGCCG?AGGATGCGCT?CAGCGCGACC?GAGCGCGCTG?44460

AGCGCGGCTC?CTACGTGGAG?TGCATCGCCG?GAGCGCTGAC?CTTCGCCGAG?TACCGCCGCG?44520

GCCTGGAACG?GGCCGGGTTC?GCCGACGTCG?ACATCACCGC?GACCCACCAG?GTGGCCGACG?44580

GGATGCACTC?GGCGATCGTG?CGGGCGGTCA?AGCCCGCCAC?CGGGCCGGTC?GCCGAGCCCG?44640

CGGCCGTCGC?GGCCTCCGGA?TCGTGCTGCG?GGGTGAGCGC?GTGCTGCACG?CCTGCCGAGT?44700

CGGCGCTGGA?CCGGTCGAGC?ACGGTGGCCG?AAGCGAAGGC?CGCTTCCGGT?TGCGGCTGCC?44760

AGAGCTGAGC?ACGTGCGGGC?GGGCCCGCGG?TGCGGACTCG?GAAGGCAGGC?CCACCGCGGG?44820

CGCGCCCCCG?CGACGCCGCA?CCGCCGGGCC?TGGCGGTGCC?AAGGTCCGTC?TATGGTTTGA?44880

CCGACTCGGG?TAGCGCAGCA?CCGGCCATCC?GCGGTGTTCC?GGCGATGGCA?CGGCGGTCCA?44940

GGTGCCGATG?GAAGGAACAC?CCCTGTGACG?ACCAGGCCGC?GGATCACGGC?GTCGGCGCTG?45000

ACCCTGGCGG?GCGCCCTGGT?GCTGTCCGCC?TGTGGCAGCG?ACGACAACCG?GGACACGATC?45060

AAGTGGACCC?TCGACAAGGG?GAACGTTCCG?GTTCCCACCG?CGACGATCCC?GATCGACTGC?45120

GGCGGCACGC?GAGCACTGAC?CGGCGAGGGC?TCCACCGCCC?AGAAGGGCGC?GATGGACGTG?45180

TTCGTCGCCG?CCTACACCCA?GCAGTGCCCC?GGCCAGCAGA?TGGCGTACAC?GGCCAGCGGC?45240

TCGGGCGCGG?GGGTCAAGCA?GTTCCTCGCC?GGGCTGGTCG?ACATCGGCGG?CAGCGACTCG?45300

GCGCTCAAGC?CGGAGCGGGG?CGAGGTCACC?GACGCCGCCG?CGCGCTGCGG?CGGCAACCCG?45360

GCCTGGAACC?TGCCCCTGGT?GTTCGGTCCG?GTCGCCGTGG?TCTACCAGAT?CCGATATCTC?45420

TAGAGCCGCC?CGCAGGACGC?TTCCGCAAGG?CAGCTTTCTG?GACCACTCCG?GAAGCGGTCC?45480

TCCGTTGCTG?TCGAAGGGAC?CCTGTCCGCC?CTGGGAGATC?TGGCAGCCCG?GGCCCCCGCT?45540

TTTCGCGTCT?TGATCGGGAC??45560

<210>2

<211>49

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Ala?Asp?Leu?Ser?Ala?Leu?Asn?Ile?Asp?Ser?Leu?Glu?Ile?Ser

1???????????????5???????????????????10??????????????????15

Glu?Phe?Leu?Asp?Asp?Ser?Arg?Leu?Glu?Asp?Ser?Glu?Val?Val?Ala?Lys

20??????????????????25??????????????????30

Val?Met?Ser?Ala?Ser?Cys?Thr?Thr?Cys?Glu?Cys?Ser?Cys?Ser?Cys?Ser

35??????????????????40??????????????????45

Ser

<210>3

<211>631

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Ala?Ala?Pro?Gln?Val?Ala?Gly?Thr?Gly?Phe?Leu?Ala?Asp?Glu?Leu

1???????????????5???????????????????10??????????????????15

Gly?Arg?Arg?Leu?Ser?Ala?Asp?Pro?Pro?Ala?Gly?Val?Asp?Thr?Val?Leu

20??????????????????25??????????????????30

Val?Ala?Glu?Leu?Asp?Arg?Ile?Gly?Glu?His?His?Asp?Leu?Ile?Val?Glu

35??????????????????40??????????????????45

Cys?Leu?Gly?Thr?Gly?Arg?Pro?Leu?Leu?Phe?Val?Gly?Thr?Tyr?Arg?Ser

50??????????????????55??????????????????60

Leu?Val?Tyr?Ile?Gly?Pro?Leu?Trp?Ala?Ser?Arg?Val?Pro?Gly?Cys?Pro

65??????????????????70??????????????????75??????????????????80

His?Cys?Leu?Val?Thr?Arg?Thr?Ala?Asn?Ser?Pro?Phe?Gly?Pro?Asp?Leu

85??????????????????90??????????????????95

Arg?Gly?Asp?Thr?Ala?Pro?Glu?Ser?Ser?Arg?Arg?Asp?Thr?Ala?Thr?Phe

100?????????????????105?????????????????110

Thr?Leu?Gly?Pro?Gly?Val?Leu?Ala?Ala?Val?Glu?Arg?Leu?Val?Arg?Glu

115?????????????????120?????????????????125

Arg?Met?Ala?Asp?Ser?Gly?Pro?Asp?Gly?Pro?Gly?Ser?Pro?Asp?Cys?Glu

130?????????????????135?????????????????140

Val?Thr?Val?Val?Asp?Gly?Val?Thr?Ala?Thr?Val?Asp?Arg?Gln?Val?Leu

145?????????????????150?????????????????155?????????????????160

Leu?Pro?Asp?Ser?Thr?Cys?Ala?Ser?Cys?Gly?Gly?Ala?Glu?Ala?Asp?Thr

165?????????????????170?????????????????175

Val?Pro?Val?Phe?Thr?Pro?Arg?Glu?Val?Pro?Leu?Pro?Lys?Leu?Gly?Pro

180?????????????????185?????????????????190

Arg?Ser?Leu?Arg?Thr?Ala?Glu?Leu?Asp?Ala?Asp?Thr?Val?Ala?Lys?Asp

195?????????????????200?????????????????205

Tyr?Leu?Phe?Ala?Gly?Ile?Gly?Leu?Phe?Lys?Glu?Val?Arg?Gln?Asp?Leu

210?????????????????215?????????????????220

Gln?Ser?Pro?Ile?Gly?Ala?Cys?Ser?Val?Glu?Leu?Gly?Thr?Arg?Trp?Gly

225?????????????????230?????????????????235?????????????????240

Arg?Arg?Glu?Pro?Ala?Ile?Gly?Arg?Gly?Arg?Thr?Tyr?Arg?Ser?Ser?Arg

245?????????????????250?????????????????255

Thr?Ile?Ala?Val?Leu?Glu?Gly?Leu?Glu?Arg?Tyr?Ala?Gly?Leu?His?Arg

260?????????????????265?????????????????270

Gly?Gly?Arg?Ser?Ala?Pro?Val?Arg?Ala?Cys?Tyr?Ala?Asp?Val?Ala?Asp

275?????????????????280?????????????????285

Arg?Ala?Ile?Asp?Pro?Thr?Thr?Leu?Gly?Thr?His?Pro?Glu?Ala?Ser?Tyr

290?????????????????295?????????????????300

Ala?Glu?Pro?Gly?Phe?Arg?Phe?Arg?Arg?Phe?Asp?Arg?Asp?Thr?Val?Val

305?????????????????310?????????????????315?????????????????320

Asp?Trp?Val?Trp?Ala?Tyr?Ser?Met?Arg?Arg?Gly?Glu?Arg?Val?Leu?Leu

325?????????????????330?????????????????335

Pro?Glu?Arg?Ala?Ala?Phe?Trp?Gly?Pro?Arg?His?Asp?Gly?Glu?Thr?Ala

340?????????????????345?????????????????350

Phe?Leu?Tyr?Asp?Thr?Ser?Asn?Gly?Cys?Ala?Leu?Gly?Asn?Ser?Ala?Glu

355?????????????????360?????????????????365

Glu?Ala?Val?Leu?His?Gly?Leu?Arg?Glu?Val?Ala?Glu?Arg?Asp?Ser?Phe

370?????????????????375?????????????????380

Leu?Met?Ala?Trp?Tyr?Arg?Arg?Leu?Ala?Leu?Pro?Glu?Ile?Asp?Met?Val

385?????????????????390?????????????????395?????????????????400

Gly?Ala?Asp?Ala?Gly?Leu?Asp?Ala?Leu?Leu?Arg?Lys?Ala?Glu?Leu?Phe

405?????????????????410?????????????????415

Thr?Gly?Phe?Arg?Phe?Arg?Ala?Phe?Leu?Ser?Thr?Met?Glu?Tyr?Arg?Met

420?????????????????425?????????????????430

Pro?Cys?Thr?Trp?Leu?Val?Ala?Glu?Ser?Arg?Leu?Asp?Asp?Gly?Pro?Arg

435?????????????????440?????????????????445

Val?Phe?Ala?Gly?Ala?Gly?Ala?His?Pro?Asp?Pro?Val?Gln?Ala?Ile?Ala

450?????????????????455?????????????????460

Gly?Gly?Leu?His?Glu?Leu?Ile?Gly?Ser?Val?Leu?Ala?Thr?Arg?His?Ser

465?????????????????470?????????????????475?????????????????480

Tyr?Glu?Arg?Arg?Arg?Ala?Asp?Gly?Leu?Ala?Met?Leu?Ala?Asp?Pro?Ala

485?????????????????490?????????????????495

Leu?Met?Thr?Arg?Met?Glu?Asp?His?Ser?Leu?Val?Gly?Ala?Leu?Pro?Glu

500?????????????????505?????????????????510

Ala?Arg?Glu?Arg?Trp?Ser?Phe?Leu?Leu?Asp?Ala?Asp?Ala?Gly?Arg?Val

515?????????????????520?????????????????525

Ala?Leu?Ala?Asp?Val?Pro?Gly?Thr?Leu?Arg?Glu?Arg?Glu?Pro?Asp?Leu

530?????????????????535?????????????????540

Arg?Ala?Asp?Leu?Asp?Val?Ala?Val?Ser?Gly?Val?Leu?Ala?Ala?Gly?Met

545?????????????????550?????????????????555?????????????????560

Asp?Val?Leu?Val?Val?Asp?Gln?Thr?Met?Pro?Glu?Leu?Arg?Arg?Asn?Gly

565?????????????????570?????????????????575

Leu?Thr?Cys?Val?Arg?Val?Val?Val?Pro?Gly?Ala?Val?Pro?Met?Thr?Phe

580?????????????????585?????????????????590

Gly?His?Arg?Asn?Arg?Arg?Thr?Arg?Asp?Leu?Pro?Arg?Leu?Ala?Gly?Gly

595?????????????????600?????????????????605

Ala?Gly?Leu?Pro?Tyr?Arg?Ser?Gly?Leu?Val?Asp?Gly?Glu?Glu?Pro?Gly

610?????????????????615?????????????????620

Cys?Val?Pro?His?Pro?Phe?Pro

625?????????????????630

<210>4

<211>479

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Thr?Gly?Asp?Leu?Ala?Glu?His?Thr?Glu?Ser?Leu?Arg?Arg?Asp?Pro

1???????????????5???????????????????10??????????????????15

Gln?Gly?Ala?Asn?Pro?Asp?Gly?Trp?Arg?Val?Asp?Trp?Ala?Asp?Gly?Pro

20??????????????????25??????????????????30

Trp?Pro?Val?Lys?Val?Tyr?Ala?Gly?Gly?Val?Arg?Thr?Pro?Leu?Gly?Arg

35??????????????????40??????????????????45

Ala?Gly?Ala?Leu?Asp?Arg?Leu?Leu?Leu?Phe?Thr?Phe?Gly?Met?Thr?Ala

50??????????????????55??????????????????60

Val?Arg?Phe?Asp?Pro?Ala?Gly?Gly?Met?Pro?Ser?Thr?Pro?Asp?Asn?Pro

65??????????????????70??????????????????75??????????????????80

Thr?Pro?Thr?His?Leu?Gly?Glu?Arg?Tyr?Ala?Pro?Arg?Arg?Pro?Ile?Pro

85??????????????????90??????????????????95

Ser?Gly?Gly?Ser?Met?Tyr?Pro?Thr?Glu?Ala?Tyr?Val?Val?Asp?Thr?Glu

100?????????????????105?????????????????110

Ala?Gly?Arg?Val?Ser?His?Tyr?Asp?Pro?Tyr?Arg?His?Glu?Leu?Val?Asp

115?????????????????120?????????????????125

Leu?Gly?Arg?Pro?Ala?Pro?Arg?Ala?Ala?Leu?Arg?Ala?Ala?Leu?Gly?Glu

130?????????????????135?????????????????140

Pro?Ala?Asp?Ala?Pro?Leu?Pro?Pro?Ala?Val?Leu?Leu?Val?Ala?Asn?Arg

145?????????????????150?????????????????155?????????????????160

Phe?Trp?Lys?Asn?Ala?Tyr?Lys?Tyr?Gly?Glu?Phe?Ala?Ala?Arg?Leu?Gly

165?????????????????170?????????????????175

Ala?Val?Asp?Thr?Gly?Val?Ala?Leu?Gly?Arg?Ala?Ala?Arg?Val?Ala?Glu

180?????????????????185?????????????????190

Ala?Ala?Phe?Gly?Asp?Ile?Ala?Val?Leu?Val?Asp?Leu?Asp?Ala?Ala?Ala

195?????????????????200?????????????????205

Val?Glu?Asp?Leu?Leu?Gly?Leu?Asp?Gly?Arg?Asp?Glu?Ala?Val?Phe?Ala

210?????????????????215?????????????????220

Ala?Val?Glu?Leu?Gly?Arg?Arg?Arg?Asp?Cys?Pro?Ala?Glu?Pro?Pro?Ala

225?????????????????230?????????????????235?????????????????240

Glu?Arg?Ala?Ala?Pro?Pro?Pro?Val?Leu?Glu?Arg?Ser?Arg?Ala?Val?Arg

245?????????????????250?????????????????255

Arg?Leu?Pro?Gly?Leu?Ser?Ala?Leu?Thr?Glu?Ala?Ala?Arg?Gln?Pro?Ala

260?????????????????265?????????????????270

Glu?Pro?Val?Ala?Val?Asp?Arg?Pro?Ala?Ala?Val?Arg?Gly?Pro?Leu?Asp

275?????????????????280?????????????????285

Leu?Leu?Asp?Pro?Gly?Val?Met?Val?Arg?Arg?Gly?Ser?His?Gly?Arg?Arg

290?????????????????295?????????????????300

Phe?Thr?Gly?Ala?Pro?Val?Arg?Leu?Ala?Asp?Val?Glu?Ala?Val?Leu?Leu

305?????????????????310?????????????????315?????????????????320

His?Ala?Ala?Glu?Ala?Ala?Ala?Arg?Leu?Ala?Ala?Val?Ser?Gly?Gly?Ala

325?????????????????330?????????????????335

Val?Gly?Ala?Glu?Ala?Gly?Leu?Cys?Cys?Ala?Val?Arg?Arg?Val?Glu?Gly

340?????????????????345?????????????????350

Leu?Ala?Pro?Gly?Trp?Tyr?Arg?Phe?Asp?Gly?Ala?Leu?Val?Pro?Val?Ala

355?????????????????360?????????????????365

Glu?Asp?Asp?Pro?Gly?Pro?Val?Leu?Arg?Arg?Ala?Leu?Phe?Ala?Glu?Ser

370?????????????????375?????????????????380

Leu?Asn?Pro?Glu?Leu?Ala?Ala?Phe?Thr?Val?His?Val?Thr?Gly?Pro?Val

385?????????????????390?????????????????395?????????????????400

Asp?Phe?Ala?Gly?Gly?Ala?Ala?Gly?Tyr?Arg?Ala?Arg?Gln?Leu?Gly?Val

405?????????????????410?????????????????415

Gly?Ala?Val?Val?Glu?Ala?Val?Cys?Leu?Ala?Ala?Thr?Ala?Ala?Arg?Leu

420?????????????????425?????????????????430

Ser?Gly?His?Ala?Val?Leu?Gly?Phe?Asp?Val?Gly?Pro?Ile?Asp?Leu?Ala

435?????????????????440?????????????????445

Tyr?Ala?Leu?Pro?Ala?Asp?Arg?Gly?Val?His?Ala?Gln?Val?Cys?Val?Gly

450?????????????????455?????????????????460

Ala?Val?Arg?Pro?Ser?Thr?His?Trp?Glu?Val?Ala?Val?Met?Pro?Arg

465?????????????????470?????????????????475

<210>5

<211>852

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Leu?Phe?Arg?Arg?Gly?Thr?Ile?Gly?Leu?Pro?Ala?Leu?Ala?Gly?Leu

1???????????????5???????????????????10??????????????????15

Val?Pro?Thr?Arg?Thr?Trp?Glu?Leu?Leu?Ala?Ala?Ala?Asp?Ala?Glu?Arg

20??????????????????25??????????????????30

Ala?Val?Arg?Glu?Pro?Leu?Arg?Ala?Arg?Leu?Ser?Asp?Ala?Leu?His?Ala

35??????????????????40??????????????????45

Val?Val?Pro?Glu?Val?Ala?Asp?Ala?Glu?Arg?Arg?Ala?Val?Leu?Lys?Leu

50??????????????????55??????????????????60

Arg?Arg?Asp?Val?His?Asn?Asp?Arg?Val?Pro?Ala?Ser?Val?Pro?Pro?Leu

65??????????????????70??????????????????75??????????????????80

Pro?Gly?Asp?Leu?Ala?Glu?Arg?Val?Gly?Glu?Trp?Val?Ala?Ala?Arg?Arg

85??????????????????90??????????????????95

Arg?Gly?Ala?Glu?Leu?Glu?Ala?Leu?Ala?Glu?Glu?Val?Tyr?Ala?Ala?Glu

100?????????????????105?????????????????110

Leu?Glu?Ser?Ala?Arg?Lys?Ala?Leu?Ala?Ala?Val?Ala?Leu?Gly?Glu?Asp

115?????????????????120?????????????????125

Phe?Gln?Arg?Gly?Val?Gln?Leu?Ser?Gly?Glu?Asp?Val?His?Arg?Glu?Val

130?????????????????135?????????????????140

Thr?Ala?Tyr?Ala?Gly?Asp?Pro?Phe?Asp?Thr?Thr?Arg?Lys?Pro?Ala?Lys

145?????????????????150?????????????????155?????????????????160

Arg?Arg?Arg?Ala?Glu?Ser?Thr?Ile?Thr?Ser?Phe?Ala?Tyr?Arg?Val?Val

165?????????????????170?????????????????175

Phe?Lys?Pro?Ser?Pro?Phe?Gly?Ala?Phe?Thr?Glu?Ile?Gly?Ala?Gln?Pro

180?????????????????185?????????????????190

Trp?Gly?Ala?Ala?Pro?Ala?Ala?Gly?Glu?Arg?Val?Ala?Arg?Ala?Arg?Leu

195?????????????????200?????????????????205

Ser?Val?Gly?Leu?Leu?Ala?Trp?Met?Thr?His?Gln?Leu?His?Arg?Val?Asp

210?????????????????215?????????????????220

Gly?Ala?Gly?Ala?Leu?Leu?Arg?Val?Arg?Leu?Asn?Asn?Ser?Leu?Ala?Val

225?????????????????230?????????????????235?????????????????240

Arg?Gly?Glu?His?Ala?Val?Ser?Val?Arg?Arg?Pro?Leu?Glu?Gly?Ala?Asp

245?????????????????250?????????????????255

Asp?Gly?Phe?Arg?Pro?Asp?Gln?Val?Ile?Arg?Ala?Lys?Asn?Ser?Pro?Leu

260?????????????????265?????????????????270

Val?Arg?Val?Leu?Val?Gly?Leu?Leu?Ala?Asp?His?Asp?Arg?Thr?Glu?Asp

275?????????????????280?????????????????285

Asp?Leu?Arg?Ala?Arg?Leu?Val?Asp?Ala?Gly?Leu?Ala?Ala?Asp?Ala?Ala

290?????????????????295?????????????????300

Ala?Gly?Thr?Ile?Asp?Gln?Leu?Val?Arg?Ala?Gly?Leu?Cys?His?Arg?Gly

305?????????????????310?????????????????315?????????????????320

Leu?Gly?Leu?Pro?Asp?Gln?Ala?Asp?Arg?Val?Ala?Glu?Glu?Val?Ala?Ser

325?????????????????330?????????????????335

Arg?Leu?Ala?Ala?Val?Gly?Thr?Ala?Gln?Ala?Leu?Ala?Cys?Ala?Glu?Val

340?????????????????345?????????????????350

Phe?Thr?Gly?Leu?Gln?Ala?Val?Glu?Asp?Ala?Phe?Ala?Asp?Ala?Pro?Ala

355?????????????????360?????????????????365

Ala?Arg?Arg?Thr?Gly?Leu?Leu?Ala?Glu?Leu?Arg?Ala?Leu?Val?Ala?Arg

370?????????????????375?????????????????380

Phe?Val?Glu?Val?Val?Gly?Cys?Pro?Pro?Pro?Ala?Arg?Glu?Ala?Met?Arg

385?????????????????390?????????????????395?????????????????400

Ala?Ala?Leu?Tyr?Glu?Asp?Val?Gly?Thr?Arg?Ala?His?Ala?Asp?Ser?Trp

405?????????????????410?????????????????415

Arg?Pro?Ala?Leu?Leu?Glu?Arg?Asp?Arg?Glu?Asn?Leu?Asp?Leu?Leu?Gln

420?????????????????425?????????????????430

Arg?Leu?Val?Pro?Leu?Leu?Asp?Asp?Ala?Ile?Val?Glu?Lys?Leu?Gly?Leu

435?????????????????440?????????????????445

Tyr?Ala?Phe?Phe?Ala?Asp?Arg?Phe?Gly?Glu?Asp?His?Ala?Gly?Val?Pro

450?????????????????455?????????????????460

Val?Val?Glu?Leu?Tyr?Glu?Ala?Phe?Ser?Ala?Leu?Ser?Pro?Ala?Glu?Ala

465?????????????????470?????????????????475?????????????????480

Ser?Ala?Val?Met?Cys?Gly?Val?Gly?Asp?Pro?His?Ala?Gln?His?Val?Leu

485?????????????????490?????????????????495

Ala?Leu?Arg?Arg?Asp?Phe?Leu?Gly?Trp?Val?Arg?Asp?Gln?Arg?Ala?Asp

500?????????????????505?????????????????510

Gly?Glu?Leu?Val?Leu?Asp?Pro?Ala?His?Leu?Ala?Ser?Val?Val?Asp?Ala

515?????????????????520?????????????????525

Leu?Pro?Pro?Thr?Val?Val?Pro?Trp?Arg?Ser?Thr?Ala?Tyr?Arg?Val?Gln

530?????????????????535?????????????????540

Gln?Ala?Asp?Asp?Leu?Thr?Val?Val?Asn?Gly?Ile?Thr?Thr?Gly?His?Gly

545?????????????????550?????????????????555?????????????????560

Val?Phe?Phe?Ser?Arg?Tyr?Cys?Asp?Leu?Leu?Gly?Gly?Gly?Arg?Phe?Asp

565?????????????????570?????????????????575

Leu?Ala?Gly?Ser?Leu?Arg?Asp?Thr?Ile?Ala?Arg?His?Thr?Pro?Arg?Gln

580?????????????????585?????????????????590

Ala?Asp?Ile?Thr?Ala?Ala?Leu?Gly?Leu?Asn?Phe?Asn?Leu?His?Pro?Arg

595?????????????????600?????????????????605

Leu?Thr?Pro?Leu?Glu?Val?Val?Tyr?Pro?Gly?Ser?Val?Gln?Arg?Pro?Gly

610?????????????????615?????????????????620

Ala?Thr?Gly?Val?Leu?Thr?Leu?Ala?Asp?Leu?Val?Val?Arg?Ala?Asp?Pro

625?????????????????630?????????????????635?????????????????640

Thr?Thr?Arg?Arg?Leu?Ala?Leu?Trp?Ser?Thr?Gln?Asp?Gly?Glu?Arg?Ile

645?????????????????650?????????????????655

Asp?Leu?Ala?Pro?Leu?Asn?Phe?Leu?Tyr?Pro?Ala?Ala?Ala?Pro?Met?Leu

660?????????????????665?????????????????670

Tyr?Arg?Phe?Leu?Cys?Ala?Phe?Ala?Pro?Thr?Arg?Thr?Tyr?Arg?Gly?Gly

675?????????????????680?????????????????685

Leu?Trp?Asp?Gln?Leu?Asp?Arg?Ala?Gly?Leu?Ala?Pro?Ala?Asp?Arg?Pro

690?????????????????695?????????????????700

Arg?Val?Arg?Leu?Gly?Gly?Leu?Val?Leu?Asp?Arg?Arg?Ser?Trp?Arg?Leu

705?????????????????710?????????????????715?????????????????720

Pro?Val?Ala?Asp?Leu?Pro?Ala?Leu?Asp?Gly?Leu?Glu?Arg?Gln?Glu?Leu

725?????????????????730?????????????????735

Thr?Ala?Leu?Ala?Glu?Phe?Asp?Ala?Trp?Arg?Arg?Ala?Ala?Gly?Leu?Pro

740?????????????????745?????????????????750

Arg?His?Ala?Phe?Phe?Arg?Val?Val?Ala?Pro?Pro?Val?Arg?Ala?Asp?Gly

755?????????????????760?????????????????765

Glu?Arg?Asp?Tyr?Ala?Ala?Glu?Thr?Arg?Glu?Trp?Ala?Leu?Gln?Ala?Arg

770?????????????????775?????????????????780

Ser?Ala?Arg?Leu?His?Lys?Pro?His?Tyr?Leu?Asp?Ala?Ala?Asn?Pro?Phe

785?????????????????790?????????????????795?????????????????800

Leu?Leu?His?Val?Leu?Ala?Lys?Gln?Ala?Arg?Ala?Thr?Pro?Gly?Gly?His

805?????????????????810?????????????????815

Val?Val?Val?Gln?Glu?Cys?Leu?Pro?Gly?Ala?Glu?Gly?Tyr?Ala?Ser?Gly

820?????????????????825?????????????????830

Ala?Gly?Ser?Ala?Glu?Glu?Phe?Phe?Val?Glu?His?Thr?Leu?Thr?Gly?Gly

835?????????????????840?????????????????845

Cys?Asp?Ala?Arg

850

<210>6

<211>330

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Trp?Arg?Ala?Leu?His?Val?His?Arg?Tyr?Ala?Asp?Gln?Asp?Thr?Leu

1???????????????5???????????????????10??????????????????15

Ile?Thr?Asp?Gly?Ile?Ala?Pro?Val?Leu?Glu?Leu?Leu?Arg?Glu?Ser?Gly

20??????????????????25??????????????????30

Ala?Ile?His?Gly?Trp?Phe?Phe?Leu?Arg?Tyr?Trp?Gln?Gly?Gly?His?His

35??????????????????40??????????????????45

Ile?Arg?Val?Arg?Met?Arg?Val?Ala?Glu?Thr?Asp?Ala?Asp?Ala?Val?Val

50??????????????????55??????????????????60

Gly?Glu?Val?Asp?Gly?Lys?Leu?Arg?Ala?Tyr?Leu?Ala?Glu?His?Pro?Ala

65??????????????????70??????????????????75??????????????????80

Ala?Glu?Gln?Phe?Asp?Ala?Glu?Glu?Phe?His?Arg?Glu?Ala?Gln?Pro?Thr

85??????????????????90??????????????????95

Met?Ala?Ala?Leu?Glu?Gly?Thr?Ala?Ala?Glu?Glu?Ile?His?Pro?Pro?Asp

100?????????????????105?????????????????110

Ser?Val?Arg?Arg?Val?Glu?Tyr?Ala?Pro?Glu?His?Asp?Lys?Tyr?Gly?Gly

115?????????????????120?????????????????125

Pro?Asp?Gly?Val?Ala?Val?Ala?Glu?Asp?Tyr?Phe?Gly?Asp?Ser?Ser?Ala

130?????????????????135?????????????????140

Ile?Val?Val?Asp?Ala?Leu?Arg?Ala?Val?Gly?Gly?Lys?Ser?Ser?Lys?Arg

145?????????????????150?????????????????155?????????????????160

Thr?Gly?Met?Gly?Tyr?Gly?Met?Met?Leu?Arg?Gly?Leu?Cys?Ala?Thr?Asp

165?????????????????170?????????????????175

Leu?Thr?Pro?Ala?Glu?Met?Ala?Ala?Phe?Phe?Ala?His?Tyr?Cys?Val?Ile

180?????????????????185?????????????????190

Trp?Ser?Pro?Tyr?Val?Phe?Asp?Gly?Phe?Leu?Asp?Ala?Trp?Pro?Ala?Leu

195?????????????????200?????????????????205

Leu?Ala?Glu?His?Ser?Ala?Pro?Leu?Arg?Ala?His?Thr?Glu?Ala?Val?Leu

210?????????????????215?????????????????220

Ala?Asn?Arg?Gly?Ala?Leu?Ala?Gly?Asp?Pro?Met?His?Asp?Ala?Val?Gly

225?????????????????230?????????????????235?????????????????240

Arg?Ala?Trp?Ala?Arg?Val?His?Glu?Ala?Gly?Pro?Ala?Val?Leu?Asp?Arg

245?????????????????250?????????????????255

Val?Arg?Leu?Ala?Gly?Asp?Asp?Ala?Ser?Ala?Ala?Arg?Arg?Ala?Gln?Val

260?????????????????265?????????????????270

Leu?Leu?Val?Ser?Tyr?Leu?His?Thr?His?Asn?Asn?Arg?Phe?Gly?Leu?Ile

275?????????????????280?????????????????285

Pro?Glu?Leu?Glu?Ala?Phe?Leu?Gly?Tyr?Leu?Gly?His?His?Val?Leu?Ser

290?????????????????295?????????????????300

Gly?Cys?Ala?Gly?Thr?Pro?Val?Asp?Ala?Gly?Leu?Glu?Ser?Arg?Val?Arg

305?????????????????310?????????????????315?????????????????320

Ser?His?Arg?Ala?Gln?Leu?Ile?Gly?Thr?Pro

325?????????????????330

<210>7

<211>366

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Leu?Ala?Leu?Gly?Pro?Asp?Asp?Glu?Pro?Gly?Ala?Ser?Arg?Pro?Ala

1???????????????5???????????????????10??????????????????15

Val?Ala?Leu?Ala?Leu?Trp?Glu?Asp?Glu?Ser?Val?Ser?Thr?Ala?Glu?Leu

20??????????????????25??????????????????30

Val?Ala?Ala?Ala?Glu?Leu?Arg?Cys?Ala?Glu?Arg?Thr?Pro?Arg?Leu?His

35??????????????????40??????????????????45

Thr?Phe?Val?Pro?Leu?Tyr?Thr?Thr?Asn?His?Cys?Asp?Ser?Glu?Cys?Lys

50??????????????????55??????????????????60

Met?Cys?Ser?Met?Arg?Lys?Gly?Asn?Ala?Arg?Met?Glu?Arg?Lys?Phe?Ser

65??????????????????70??????????????????75??????????????????80

Gly?Arg?Asp?Glu?Ile?Ile?Asp?Gln?Leu?Arg?Ile?Leu?Phe?Glu?His?Glu

85??????????????????90??????????????????95

Gly?Val?Arg?Gly?Val?Gly?Phe?Leu?Thr?Gly?Glu?Tyr?Glu?Asp?Lys?Tyr

100?????????????????105?????????????????110

Thr?Arg?Leu?Ser?Thr?Ala?Phe?Arg?Ile?Gly?Trp?Ala?Ile?Arg?Thr?Ala

115?????????????????120?????????????????125

Leu?Asp?Met?Gly?Phe?Glu?Arg?Val?Tyr?Phe?Asn?Ile?Gly?Ser?Met?Glu

130?????????????????135?????????????????140

Pro?Asp?Glu?Ile?Asp?Val?Leu?Ala?Glu?Trp?Val?Arg?Arg?Asp?Asp?Pro

145?????????????????150?????????????????155?????????????????160

Val?Thr?Met?Cys?Val?Phe?Gln?Glu?Thr?Tyr?Asp?Arg?Asp?Ser?Tyr?Ser

165?????????????????170?????????????????175

Lys?Phe?Met?Gly?Asp?Thr?Val?Ser?Gly?Val?Pro?Lys?Ala?Asp?Tyr?Asp

180?????????????????185?????????????????190

Arg?Arg?Val?Val?Ser?Phe?Asp?Arg?Trp?Leu?Asp?Lys?Gly?Phe?Arg?Tyr

195?????????????????200?????????????????205

Val?Asn?Pro?Gly?Val?Leu?Ile?Gly?Leu?His?Leu?Asp?Val?Ala?Ala?Glu

210?????????????????215?????????????????220

Leu?Val?Thr?Leu?Val?Ala?His?Gly?Ala?His?Leu?Lys?Asp?Arg?Asp?Ala

225?????????????????230?????????????????235?????????????????240

Val?Val?Asp?Leu?Ser?Val?Pro?Arg?Met?Arg?Pro?Ala?Met?Ser?Ser?Arg

245?????????????????250?????????????????255

Asp?Ser?Thr?Arg?Ile?Lys?Asp?Asp?Glu?Tyr?Met?Arg?Leu?Met?Ala?Val

260?????????????????265?????????????????270

Leu?Ala?Phe?Thr?Cys?Pro?Glu?Gln?Arg?Leu?Val?Leu?Thr?Thr?Arg?Glu

275?????????????????280?????????????????285

Pro?Gln?Glu?Phe?Gln?Asp?Gln?Ala?Ile?Gly?Leu?Ala?Gly?Val?Ile?Ser

290?????????????????295?????????????????300

Pro?Gly?Ser?Pro?Asp?Val?Ala?Pro?Tyr?Arg?Ala?Asp?Ser?Gln?Ala?Arg

305?????????????????310?????????????????315?????????????????320

Asn?Glu?Glu?Thr?Thr?Ser?Gln?Phe?Leu?Val?Ala?Asp?Leu?Arg?Arg?Pro

325?????????????????330?????????????????335

Arg?His?Ile?Leu?Gly?Arg?Ile?Glu?Ala?Gly?Gly?Thr?Lys?Val?Gly?His

340?????????????????345?????????????????350

Phe?Ala?Asn?Pro?Ser?Val?Gly?Ala?Ala?Val?Ile?Pro?Ile?Gly

355?????????????????360?????????????????365

<210>8

<211>410

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Arg?Trp?Gly?Gly?Glu?Ser?Ala?Thr?Trp?Asp?Glu?Leu?Leu?Asp?Arg

1???????????????5???????????????10??????????????????15

Gly?Arg?Glu?Arg?Ser?Ala?Leu?Val?Ala?Pro?Gln?Arg?Ala?Tyr?Arg?Val

20??????????????????25??????????????????30

Asp?Pro?Ala?Ala?Gly?Leu?Glu?Ser?Leu?Val?Ser?Leu?Phe?Ala?Val?Ala

35??????????????????40??????????????????45

Thr?Val?Ala?Asp?Thr?Val?Leu?Leu?Trp?Ser?Ser?Gly?Pro?Gly?Gly?Arg

50??????????????????55??????????????????60

Glu?Leu?Ala?Pro?Gly?Leu?Ala?Glu?Ala?Asp?Leu?Pro?Val?Asp?Gly?Pro

65??????????????????70??????????????????75??????????????????80

Leu?Glu?Arg?Pro?Leu?Trp?Gly?Val?Ala?Thr?Ser?Gly?Ser?Thr?Gly?Asn

85??????????????????90??????????????????95

Ala?Lys?Leu?Ala?Ile?Gly?His?Ala?Asp?Ser?Trp?Glu?Ser?Ile?Ala?Leu

100?????????????????105?????????????????110

His?Tyr?Glu?Arg?Ser?Leu?Tyr?Gly?Asp?Cys?Ser?Ala?Asp?Gly?Met?Pro

115?????????????????120?????????????????125

Pro?Val?Leu?Ala?Thr?Cys?Leu?Pro?Leu?Gln?Phe?Ser?Ala?Ser?Phe?Phe

130?????????????????135?????????????????140

Met?Thr?Val?Leu?Pro?Ser?Leu?Phe?Leu?Arg?Arg?Asp?Leu?Leu?Val?Phe

145?????????????????150?????????????????155?????????????????160

Pro?Ala?His?Asp?Trp?Ser?Ala?Ala?His?Ala?Glu?Ala?Ala?Glu?Arg?Asp

165?????????????????170?????????????????175

Ile?Ala?Val?Leu?Ala?Val?Pro?Ala?Leu?Ala?Ala?Ala?Ala?Cys?Leu?Thr

180?????????????????185?????????????????190

Met?Asp?Arg?Gln?Val?Asp?Ala?Ser?Arg?Ile?Thr?Leu?Phe?Leu?Gly?Gly

195?????????????????200?????????????????205

Gly?His?Leu?Gly?Ala?Glu?Arg?Val?Arg?Met?Val?Arg?Glu?Arg?Phe?Ser

210?????????????????215?????????????????220

Gly?Val?Ser?Val?Arg?Asn?Leu?Tyr?Gly?Thr?Ala?Glu?Thr?Gly?Ala?Val

225?????????????????230?????????????????235?????????????????240

Ala?Val?Asp?Gln?Asp?Pro?Gly?His?Asn?Gln?His?Val?Gly?Val?Pro?Val

245?????????????????250?????????????????255

Ala?Gly?Lys?Ala?Val?Trp?Leu?Glu?Gly?Thr?Asp?Pro?Asp?Gly?Ile?Gly

260?????????????????265?????????????????270

Ala?Val?Ala?Val?Ala?Gly?Pro?Asp?Cys?Cys?Leu?Gly?Thr?Trp?Arg?Pro

275?????????????????280?????????????????285

Gly?Glu?Ala?Leu?Arg?Arg?Asn?Gly?Gly?Tyr?Val?Ala?Ser?Thr?Asp?Tyr

290?????????????????295?????????????????300

Gly?Arg?Phe?Asp?Ala?Glu?Gly?Arg?Leu?Cys?Leu?Glu?Gly?Arg?Val?Asp

305?????????????????310?????????????????315?????????????????320

Gly?Gly?Glu?Lys?Leu?His?Gly?Val?Leu?Val?Tyr?Pro?Arg?Ala?Val?Glu

325?????????????????330?????????????????335

Arg?His?Leu?Leu?Ala?Leu?Pro?Gly?Val?Ala?Asp?Ala?Lys?Val?Ala?Ile

340?????????????????345?????????????????350

His?Arg?Ala?Asp?Thr?Gly?Leu?Glu?His?Leu?Val?Ala?Arg?Val?Val?Gly

355?????????????????360?????????????????365

Ser?Ala?Ser?Ala?Asp?Asp?Val?Arg?Glu?His?Cys?Ala?Ala?Leu?Pro?Glu

370?????????????????375?????????????????380

Ala?Glu?Arg?Pro?Ser?Arg?Val?Glu?Cys?Val?Pro?Glu?Glu?Leu?Ala?Leu

385?????????????????390?????????????????395?????????????????400

Ala?Ala?Tyr?Ser?Pro?Asn?Gly?Lys?Leu?Ser

405?????????????????410

<210>9

<211>295

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Arg?Glu?Ala?Ala?Gly?Asp?Gly?Ser?Ser?Pro?Val?Tyr?Phe?Leu

1???????????????5???????????????????10??????????????????15

His?Gly?Leu?Leu?Gly?Thr?Ala?Tyr?Gly?His?Phe?Gly?Ala?Gln?Ile?Ala

20??????????????????25??????????????????30

Ala?Trp?Ser?Gly?Arg?Arg?Arg?Val?Val?Pro?Val?Asp?Leu?Pro?Gly?His

35??????????????????40??????????????????45

Gly?Arg?Cys?Pro?Val?Asp?Ala?Gly?Pro?Asp?Tyr?Leu?Asp?Thr?Ala?Leu

50??????????????????55??????????????????60

Glu?Tyr?Val?Ala?Ala?Leu?Val?Asp?His?Phe?Gly?Pro?Gly?His?Leu?Val

65??????????????????70??????????????????75??????????????????80

Ala?Ala?Ser?His?Leu?Gly?Gly?Pro?Leu?Ala?Val?Arg?Leu?Ala?Glu?Ala

85??????????????????90??????????????????95

Arg?Pro?Glu?Leu?Val?Glu?Ser?Leu?Val?Leu?Thr?Gly?Phe?Phe?Pro?Gly

100?????????????????105?????????????????110

Ala?Asp?Arg?Glu?Ser?Phe?Ala?Arg?Leu?Leu?Asp?Gly?Phe?Gly?Val?Leu

115?????????????????120?????????????????125

Val?Glu?Glu?Asn?Pro?Glu?Leu?Ala?Ala?Glu?Tyr?Asp?Arg?Leu?His?Pro

130?????????????????135?????????????????140

Gly?Arg?Trp?Arg?Thr?Thr?Leu?Ala?Glu?Phe?Ser?Gly?His?Ala?Thr?Ala

145?????????????????150?????????????????155?????????????????160

Glu?Phe?Asp?Asp?Arg?Ala?Arg?Ile?Ala?Ala?Glu?Arg?Leu?Gly?Ala?Leu

165?????????????????170?????????????????175

Gly?Cys?Asp?Val?Leu?Leu?Val?Asn?Gly?Thr?Leu?Lys?Ser?Ala?Glu?Arg

180?????????????????185?????????????????190

Glu?Ala?Ala?Leu?Ala?Ala?Arg?Ser?Tyr?Gly?Pro?Arg?Val?His?Gly?Val

195?????????????????200?????????????????205

Leu?Leu?Asp?Gly?Ala?Gly?His?Ile?Ala?Ser?His?Asp?Ala?Pro?Glu?Ala

210?????????????????215?????????????????220

Phe?Thr?Ala?Ala?Val?Glu?Glu?Phe?Trp?Leu?Gly?Ala?Ala?Leu?Arg?Ala

225?????????????????230?????????????????235?????????????????240

Leu?Leu?Arg?Glu?Asn?Asp?Pro?Ala?Arg?Pro?Leu?Asp?Ser?Leu?Glu?Ser

245?????????????????250?????????????????255

Val?Thr?Ala?Leu?Ser?Tyr?Leu?Thr?Arg?Lys?Gly?Leu?Ala?Gln?Arg?Glu

260?????????????????265?????????????????270

Pro?Ala?Gly?Asp?Arg?Pro?Ser?Thr?Ile?Glu?Gly?Trp?Val?Ala?Trp?Ala

275?????????????????280?????????????????285

Leu?Arg?Arg?Ser?Leu?Val?Ser

290?????????????????295

<210>10

<211>420

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Thr?Ala?Val?Ser?Leu?Ser?Ser?Leu?Val?Asp?Val?Val?Pro?Ala

1???????????????5???????????????????10??????????????????15

Pro?Ala?Pro?Asn?Leu?Pro?Ser?Ser?Thr?Asp?Glu?Gln?His?Met?Leu?Met

20??????????????????25??????????????????30

Leu?Tyr?Val?His?Val?Pro?Phe?Cys?His?Ser?Lys?Cys?Thr?Phe?Cys?Asp

35??????????????????40??????????????????45

Trp?Val?Gln?Ala?Ile?Pro?Thr?Lys?Asp?Leu?Leu?Arg?Lys?Pro?Glu?Asp

50??????????????????55??????????????????60

Ser?Val?Arg?Lys?Asn?Tyr?Ile?Arg?Ala?Leu?Val?Thr?Glu?Ile?Glu?Thr

65??????????????????70??????????????????75??????????????????80

Arg?Gly?Ala?Gln?Leu?Arg?Ala?Ala?Gly?Gln?Val?Pro?Tyr?Val?Val?Tyr

85??????????????????90??????????????????95

Trp?Gly?Gly?Gly?Thr?Ala?Ser?Ser?Leu?Asp?Asn?Ala?Glu?Ala?Glu?Ala

100?????????????????105?????????????????110

Ile?Trp?Gly?Ala?Leu?Asp?Ser?Ala?Phe?Asp?Leu?Ser?Thr?Val?Ala?Glu

115?????????????????120?????????????????125

Ala?Thr?Ile?Glu?Cys?Ser?Pro?Asp?Thr?Val?Asp?Lys?Ala?Lys?Leu?Glu

130?????????????????135?????????????????140

Phe?Phe?Arg?Gly?Leu?Gly?Phe?Asn?Arg?Val?Ser?Ser?Gly?Val?Gln?Ser

145?????????????????150?????????????????155?????????????????160

Phe?Asp?Asp?Ala?Arg?Leu?Arg?Arg?Leu?Gly?Arg?Arg?His?Thr?Ala?Gly

165?????????????????170?????????????????175

Glu?Ala?Asp?Arg?Ile?Val?His?His?Ala?Arg?Glu?Ala?Gly?Phe?Asp?Glu

180?????????????????185?????????????????190

Val?Ser?Ile?Asp?Ile?Met?Ser?Gly?Phe?Pro?Asp?Gln?Glu?Leu?Asp?Glu

195?????????????????200?????????????????205

Leu?Arg?Ala?Thr?Val?Glu?Lys?Ala?Val?Ser?Leu?Pro?Leu?Thr?His?Leu

210?????????????????215?????????????????220

Ser?Leu?Tyr?Ser?Phe?Arg?Pro?Thr?Pro?Gly?Thr?Phe?Met?Arg?Arg?Lys

225?????????????????230?????????????????235?????????????????240

Leu?Ala?Gly?Thr?Glu?Lys?Arg?Ala?Tyr?Leu?Arg?Lys?Gln?Gln?Ala?Leu

245?????????????????250?????????????????255

Phe?Thr?Glu?Ala?Arg?Arg?Met?Ile?Ile?Asp?Ala?Gly?Leu?Pro?Glu?Tyr

260?????????????????265?????????????????270

Ala?Ser?Gly?Tyr?Phe?Gly?Arg?Val?Ser?Pro?Phe?Ala?Ala?Met?Tyr?Phe

275?????????????????280?????????????????285

Gln?Leu?Arg?Ala?Asp?Thr?Ala?Gly?Phe?Gly?Ser?Gly?Ala?Ile?Ser?Leu

290?????????????????295?????????????????300

Val?Asp?Arg?Gln?Phe?Leu?Ser?His?Ala?Lys?Gly?Lys?Leu?His?Ala?Tyr

305?????????????????310?????????????????315?????????????????320

Ile?Gln?Asp?Pro?Leu?Ala?Tyr?Asp?Ile?Asp?Val?Pro?Ala?Gly?Gln?Asp

325?????????????????330?????????????????335

Arg?Val?Leu?Val?Ser?Phe?Leu?Gln?Ala?Gly?Leu?Ala?Met?Phe?Asp?Gly

340?????????????????345?????????????????350

Val?Leu?Arg?Glu?Glu?Trp?Arg?Val?Ser?Thr?Gly?Thr?Asp?Leu?Asp?Glu

355?????????????????360?????????????????365

Val?Leu?Thr?Arg?Pro?Ser?Ile?Ala?Pro?Leu?Ala?Asp?Phe?Leu?Arg?Gly

370?????????????????375?????????????????380

Arg?Gly?Leu?Ile?Glu?Asp?Glu?Arg?Gly?Ile?Arg?Leu?Asp?Pro?Arg?Leu

385?????????????????390?????????????????395?????????????????400

Ala?Gly?Leu?Thr?Leu?Ile?Glu?Leu?Ala?Phe?Glu?Met?Ala?Met?Ser?Gln

405?????????????????410?????????????????415

Pro?Glu?Ser?Ala

420

<210>11

<211>420

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Thr?Tyr?Gly?His?Ala?His?Ala?Glu?His?Tyr?Asp?Leu?Val?Phe?Arg

1???????????????5???????????????????10??????????????????15

Ser?Arg?Gly?Lys?Asp?Trp?Pro?Ala?Glu?Ser?Ala?Arg?Ile?Ala?Ala?Leu

20??????????????????25??????????????????30

Val?Arg?Asp?Arg?Ala?Pro?Ala?Ala?Ala?Thr?Leu?Leu?Asp?Val?Gly?Cys

35??????????????????40??????????????????45

Gly?Thr?Gly?Ala?His?Leu?Val?Thr?Phe?Ala?Lys?Thr?Phe?Ala?Ala?Val

50??????????????????55??????????????????60

Ala?Gly?Val?Glu?Pro?Ala?Glu?Ala?Met?Arg?Glu?Ile?Ala?Ala?Asp?Arg

65??????????????????70??????????????????75??????????????????80

Ile?Gly?Ala?Gly?Gln?Val?His?Pro?Gly?Asp?Met?Arg?Ala?Phe?Asp?Leu

85??????????????????90??????????????????95

Gly?Arg?Thr?Phe?Asp?Ala?Val?Thr?Cys?Leu?Gly?Phe?Ala?Ile?Ala?Tyr

100?????????????????105?????????????????110

Met?Pro?Asp?Thr?Ala?Ala?Leu?Asp?Ala?Ala?Val?Ala?Arg?Met?Ala?Ala

115?????????????????120?????????????????125

His?Leu?Ser?Pro?Gly?Gly?Val?Leu?Val?Val?Glu?Pro?Trp?Trp?Gly?Pro

130?????????????????135?????????????????140

Glu?Glu?Phe?Ile?Asp?Gly?Tyr?Val?Gly?Gly?His?Leu?Val?Arg?Glu?Asp

145?????????????????150?????????????????155?????????????????160

Gly?Leu?Val?Ile?Ser?Arg?Val?Thr?His?Ser?Val?Arg?Arg?Asp?Gly?Ala

165?????????????????170?????????????????175

Thr?His?Met?Arg?Ile?His?Phe?Val?Val?Ala?Asp?Ala?Asp?Gly?Ile?Arg

180?????????????????185?????????????????190

Thr?Phe?His?Glu?Asp?Glu?Thr?Asn?Thr?Leu?Phe?Thr?Asp?Ala?Gln?Tyr

195?????????????????200?????????????????205

Arg?Ala?Ala?Phe?Glu?Arg?Ala?Gly?Leu?Ala?Val?Thr?Arg?Val?His?Asp

210?????????????????215?????????????????220

Arg?Asp?Ala?His?Pro?Gly?Tyr?Leu?Val?Gly?Val?Lys?Gly

225?????????????????230?????????????????235

<210>12

<211>414

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Thr?Gln?His?Asp?Arg?Ser?Leu?Thr?Gly?Met?Gly?Ala?Cys?Arg?Leu

1???????????????5???????????????????10??????????????????15

Cys?Ser?Gly?Pro?Val?Arg?Glu?Phe?Phe?Asp?Phe?Gly?Arg?Gln?Pro?Val

20??????????????????25??????????????????30

Ser?Asp?Ala?Phe?Arg?Asp?Pro?Ala?Asp?Thr?Ser?Pro?Glu?Phe?His?Tyr

35??????????????????40??????????????????45

Asp?Leu?Arg?Ile?Gly?Val?Cys?Gly?Gly?Cys?Ala?Met?Val?Gln?Gln?Leu

50??????????????????55??????????????????60

Thr?Glu?Val?Pro?Arg?Ala?Gln?Met?Phe?His?Ser?Glu?Tyr?Pro?Tyr?Arg

65??????????????????70??????????????????75??????????????????80

Ser?Ser?Leu?Ser?Ser?Gly?Ser?Arg?Lys?His?Phe?Glu?Ala?Tyr?Ala?His

85??????????????????90??????????????????95

His?Leu?Leu?Asp?Thr?Arg?Leu?Ala?Gly?Ala?Asp?Pro?Phe?Val?Val?Glu

100?????????????????105?????????????????110

Ile?Gly?Cys?Asn?Asp?Gly?Val?Met?Leu?Arg?Thr?Ile?Gly?Gly?Ala?Gly

115?????????????????120?????????????????125

Val?Arg?His?Leu?Gly?Phe?Glu?Pro?Ser?Gly?Gly?Ala?Ala?Asp?Ser?Ala

130?????????????????135?????????????????140

Arg?Ala?Ala?Gly?Val?Ser?Val?Val?Val?Asp?Phe?Phe?Glu?Glu?Arg?Thr

145?????????????????150?????????????????155?????????????????160

Ala?Arg?Ala?Ala?Arg?Ala?Glu?His?Gly?Pro?Ala?Asp?Val?Val?Phe?Ser

165?????????????????170?????????????????175

Ala?Asn?Thr?Val?Ser?His?Ile?Ala?Tyr?Leu?Asp?Ser?Ile?Phe?Ala?Gly

180?????????????????185?????????????????190

Val?Asp?Ala?Leu?Leu?Ala?Pro?Asp?Gly?Val?Phe?Val?Val?Glu?Asp?Arg

195?????????????????200?????????????????205

Tyr?Leu?Gly?Asp?Ile?Val?Ala?Asn?Thr?Ala?Phe?Asp?Gln?Val?Tyr?Asp

210?????????????????215?????????????????220

Glu?His?Phe?Tyr?Leu?Phe?Ser?Val?Thr?Ser?Val?Arg?Asn?Leu?Ala?Arg

225?????????????????230?????????????????235?????????????????240

Arg?Phe?Gly?Phe?Glu?Leu?Val?Asp?Ile?Thr?Arg?Leu?Pro?Val?His?Gly

245?????????????????250?????????????????255

Gly?Thr?Ile?Arg?Phe?Thr?Ile?Ala?Arg?Ala?Gly?Ala?Glu?Pro?Ser?Ala

260?????????????????265?????????????????270

Ala?Val?Thr?Glu?Arg?Leu?His?Ala?Glu?Gln?Ala?Gly?Gly?Leu?Ala?Asp

275?????????????????280?????????????????285

Pro?Ala?Thr?Leu?Glu?Ala?Phe?Gly?Gly?Arg?Val?Arg?His?Ala?Arg?Asp

290?????????????????295?????????????????300

Glu?Leu?Val?Ala?Leu?Leu?Arg?Gly?Leu?Arg?Ala?Glu?Gly?Arg?Ser?Val

305?????????????????310?????????????????315?????????????????320

Val?Gly?Tyr?Gly?Ala?Thr?Ala?Lys?Ser?Ala?Thr?Thr?Ile?Asn?Tyr?Cys

325?????????????????330?????????????????335

Gly?Ile?Thr?Pro?Glu?Leu?Val?Pro?Tyr?Ile?Cys?Asp?Ser?Thr?Pro?Glu

340?????????????????345?????????????????350

Lys?His?Gly?Lys?Leu?Ala?Pro?Gly?Ser?Gly?Ile?Pro?Val?Arg?Ser?Ser

355?????????????????360?????????????????365

Ser?Ala?Phe?Ala?Glu?Pro?Tyr?Pro?Asp?Tyr?Ala?Leu?Leu?Phe?Ala?Trp

370?????????????????375?????????????????380

Asn?His?Thr?Glu?Glu?Ile?Leu?Ala?Lys?Glu?His?Ala?Phe?Thr?Glu?Ala

385?????????????????390?????????????????395?????????????????400

Gly?Gly?Arg?Trp?Ile?Thr?Tyr?Val?Pro?Glu?Val?Arg?Val?Ile

405?????????????????410

<210>13

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<400>1

Val?Leu?Gly?Cys?Ala?Asp?Ile?Ala?Arg?Arg?Arg?Ala?Leu?Pro?Ala?Leu

1???????????????5???????????????????10??????????????????15

Ala?Ala?Cys?Ala?Ser?Thr?Val?Thr?Val?Ala?Val?Ala?Ser?Arg?Ser?Ala

20??????????????????25??????????????????30

Ala?Lys?Ala?Ala?Ala?Phe?Gly?Ala?Glu?Phe?Gly?Cys?Ala?Ala?Val?His

35??????????????????40??????????????????45

Gly?Tyr?Arg?Ala?Leu?Leu?Ala?Asp?Asp?Ala?Val?Glu?Ala?Val?Tyr?Ile

50??????????????????55??????????????????60

Ala?Val?Pro?Thr?Gly?Leu?His?Ala?Glu?Trp?Ala?Ala?Glu?Ala?Leu?Ala

65??????????????????70??????????????????75??????????????????80

Ala?Gly?Lys?His?Val?Leu?Val?Glu?Lys?Pro?Met?Ala?Ala?Thr?Ala?Ala

85??????????????????90??????????????????95

Asp?Ala?Ala?Ala?Leu?Ala?Glu?Arg?Ala?Glu?Arg?Ala?Gly?Leu?Val?Leu

100?????????????????105?????????????????110

Met?Glu?Asn?Arg?Met?Phe?Thr?Arg?His?Pro?Gln?His?Arg?Val?Val?Arg

115?????????????????120?????????????????125

Asp?Ala?Val?Ala?Arg?Gly?Glu?Ile?Gly?Leu?Pro?Arg?Val?Leu?Ser?Ala

130?????????????????135?????????????????140

Gly?Met?Thr?Ile?Pro?Pro?Arg?Pro?Ala?Asp?Asp?Ile?Arg?Tyr?Arg?Ala

145?????????????????150?????????????????155?????????????????160

Asp?Leu?Gly?Gly?Gly?Ala?Leu?Leu?Asp?Val?Gly?Tyr?Tyr?Pro?Leu?His

165?????????????????170?????????????????175

Thr?Ala?Leu?Leu?Leu?Leu?Gly?His?Asp?Val?Arg?Leu?Asp?Gly?Ala?Val

180?????????????????185?????????????????190

Val?Glu?Arg?Asp?Glu?Arg?Leu?Gly?Val?Asp?Leu?Gly?Gly?Ala?Leu?Leu

195?????????????????200?????????????????205

Leu?Ser?Thr?Ala?Arg?Gly?Ala?Val?Ala?His?Leu?Thr?Phe?Gly?Ile?Asp

210?????????????????215?????????????????220

His?His?Tyr?Arg?Ala?Ala?Tyr?Glu?Leu?Cys?Gly?Thr?Ala?Gly?Ala?Val

225?????????????????230?????????????????235?????????????????240

Thr?Ala?Ala?Arg?Ala?Tyr?Thr?Pro?Pro?Pro?Ser?Ala?Ala?Thr?Glu?Val

245?????????????????250?????????????????255

Val?Leu?Glu?Arg?Pro?Gly?Gly?Ser?Arg?Arg?Val?Gly?Ile?Ala?Pro?Phe

260?????????????????265?????????????????270

Asp?Gln?Phe?Ala?Ala?Val?Met?Ala?Glu?Phe?Ala?Ser?Ala?Val?Arg?Gly

275?????????????????280?????????????????285

Gly?Thr?Arg?Ser?Ala?Asp?His?Leu?Ala?Gly?Glu?Leu?Ala?Val?Ser?Val

290?????????????????295?????????????????300

Arg?Ala?Leu?Glu?Leu?Leu?Asp?Glu?Ala?Arg?Asp?Arg?Ala?Gln?His?Arg

305?????????????????310?????????????????315?????????????????320

Ser?Asn?Ala?Ala?Ile?Thr?Pro?Leu

325

<210>14

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<400>1

Met?Leu?Ala?Arg?Gly?Ala?Ile?Gly?Ala?Arg?Leu?Ala?Glu?Ser?Ala?Ala

1???????????????5???????????????????10??????????????????15

Ser?Gly?Pro?Thr?Ala?Val?Glu?Pro?Pro?Asp?Val?His?Ala?Trp?Leu?Ala

20??????????????????25??????????????????30

Glu?Gln?Arg?Glu?Arg?Ala?Trp?Met?His?Val?Glu?Arg?Val?Pro?Leu?Ala

35??????????????????40??????????????????45

Asp?Leu?Arg?Gly?Trp?Ala?Ala?Asp?Pro?Glu?Thr?Gly?Asp?Ile?Gly?His

50??????????????????55??????????????????60

Arg?Ser?Gly?Lys?Phe?Phe?Thr?Val?His?Gly?Ile?Asp?Val?Arg?Asp?Pro

65??????????????????70??????????????????75??????????????????80

Ala?Gly?Pro?Val?Pro?Gly?Trp?Ser?Gln?Pro?Ile?Ile?Asn?Gln?Pro?Glu

85??????????????????90??????????????????95

Val?Gly?Val?Leu?Gly?Ile?Ala?Val?Ala?Glu?Phe?Asp?Gly?Val?Leu?His

100?????????????????105?????????????????110

Leu?Leu?Met?Gln?Ala?Lys?Ala?Glu?Pro?Gly?Asn?Cys?Asn?Gly?Val?Gln

115?????????????????120?????????????????125

Leu?Ser?Pro?Thr?Val?Gln?Ala?Thr?Arg?Ser?Asn?Tyr?Thr?Arg?Val?His

130?????????????????135?????????????????140

Gly?Gly?Ala?Ala?Val?Pro?Tyr?Leu?Glu?His?Phe?Leu?Glu?Pro?Asp?Pro

145?????????????????150?????????????????155?????????????????160

Ala?Arg?Val?Ile?Ala?Asp?Val?Arg?Gln?Ser?Glu?Gln?Gly?Ala?Trp?Phe

165?????????????????170?????????????????175

Leu?Arg?Lys?Arg?Asn?Arg?Asn?Met?Val?Ile?Glu?Leu?Asp?Ser?Ser?Glu

180?????????????????185?????????????????190

Leu?Asp?Ser?Ser?Glu?Leu?Asp?Ser?Ser?Glu?Val?Asp?Ser?Gly?Gly?Ala

195?????????????????200?????????????????205

Asp?Gly?Ser?Thr?Ala?Ala?Arg?Asp?Gly?Phe?Cys?Trp?Leu?Thr?Leu?Ala

210?????????????????215?????????????????220

Thr?Val?Arg?Arg?Leu?Leu?Ala?Glu?Asp?Asp?Leu?Ile?Asn?Met?Asp?Ala

225?????????????????230?????????????????235?????????????????240

Arg?Thr?Val?Leu?Ser?Cys?Leu?Pro?Leu?Pro?Leu?Pro?Gly?Glu?Ala?Asp

245?????????????????250?????????????????255

Asp?Gly?Ser?Leu?His?Pro?Thr?Arg?Glu?Leu?Leu?Ser?Trp?Ile?Thr?Ser

260?????????????????265?????????????????270

Ala?Arg?Thr?Ala?Ala?Glu?Ile?Asp?Val?Arg?Arg?Ser?Pro?Leu?Arg?Gly

275?????????????????280?????????????????285

Leu?Thr?Gly?Trp?Ser?Gln?Ala?Asp?Gly?Ala?Ile?Arg?His?Asp?Ser?Gly

290?????????????????295?????????????????300

Leu?Phe?Phe?Glu?Val?Val?Gly?Val?Ser?Val?Arg?Ala?Cys?Gly?Arg?Glu

305?????????????????310?????????????????315?????????????????320

Val?Ala?Glu?Trp?Thr?Gln?Pro?Met?Leu?Ala?Val?Arg?Asp?Val?Gly?Leu

325?????????????????330?????????????????335

Val?Ala?Phe?Leu?Val?Arg?Arg?Ile?Gly?Gly?Val?Gln?His?Ala?Leu?Leu

340?????????????????345?????????????????350

Gln?Val?Arg?Pro?Glu?Pro?Gly?Cys?Leu?Asp?Val?Ala?Glu?Leu?Ala?Pro

355?????????????????360?????????????????365

Thr?Val?Gln?Cys?Thr?Pro?Ala?Asn?Tyr?Gly?Phe?Leu?Pro?Ala?Glu?Ala

370?????????????????375?????????????????380

Arg?Pro?Arg?Phe?Leu?Asp?Ala?Val?Leu?Ser?Ala?Pro?Ala?Glu?Arg?Val

385?????????????????390?????????????????395?????????????????400

Leu?Phe?Asp?Ala?Thr?Met?Ser?Glu?Glu?Gly?Gly?Arg?Phe?Tyr?His?Ala

405?????????????????410?????????????????415

Arg?Thr?Arg?Tyr?Leu?Val?Val?Glu?Asp?Ser?Ala?Ala?Asp?Thr?Gly?Pro

420?????????????????425?????????????????430

Thr?Gly?Asp?Leu?Glu?Arg?Ala?Gly?Phe?Lys?Trp?Val?Ala?Leu?His?Gln

435?????????????????440?????????????????445

Ala?Ala?Asp?Leu?Val?Arg?His?Ser?His?Tyr?Leu?Asn?Ile?Gln?Ala?Arg

450?????????????????455?????????????????460

Ser?Leu?Leu?Ala?Cys?Leu?Pro?Gly?Arg?Ala?Asp?Gly

465?????????????????470?????????????????475

<210>15

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<400>1

Val?Phe?Gln?Pro?Ser?Leu?Gly?Ala?Glu?Glu?Leu?Ala?Ala?Val?Gly?Glu

1???????????????5???????????????????10??????????????????15

Val?Phe?Ala?Ser?Asn?Trp?Val?Gly?Lys?Gly?Pro?Arg?Val?Ala?Glu?Phe

20??????????????????25??????????????????30

Glu?Ala?Arg?Phe?Ala?Ala?His?Leu?Gly?Val?Gly?Gly?Gly?His?Leu?Met

35??????????????????40??????????????????45

Ser?Ala?Asp?Thr?Cys?Thr?Glu?Ala?Thr?Phe?Leu?Ala?Met?Arg?Leu?Ala

50??????????????????55??????????????????60

Gly?Val?Gly?Pro?Gly?Asp?Asp?Val?Val?Leu?Pro?Thr?Val?Cys?Phe?Val

65??????????????????70??????????????????75??????????????????80

Ser?Ala?Ala?Asn?Ala?Val?Ala?Ala?His?Gly?Ala?Arg?Pro?Val?Phe?Cys

85??????????????????90??????????????????95

Asp?Val?Asp?Pro?Arg?Thr?Leu?Asn?Pro?Thr?Ala?Glu?His?Val?Glu?Ala

100?????????????????105?????????????????110

Ala?Leu?Thr?Pro?Ala?Thr?Lys?Ala?Val?Val?Val?Leu?His?Tyr?Gly?Gly

115?????????????????120?????????????????125

His?Pro?Gly?Gln?Val?Asp?Arg?Ile?Ala?Ala?Leu?Cys?Thr?Glu?Arg?Gly

130?????????????????135?????????????????140

Leu?Leu?Leu?Ile?Glu?Asp?Ala?Ala?Asn?Ala?Pro?Ala?Ser?Ala?Ile?Gly

145?????????????????150?????????????????155?????????????????160

Asp?Arg?Ala?Cys?Gly?Thr?Phe?Gly?Asp?Phe?Gly?Val?Trp?Ser?Phe?Asp

165?????????????????170?????????????????175

His?Gly?Lys?Ile?Ala?Val?Ser?Val?Asp?Gly?Gly?Met?Leu?His?Ala?Arg

180?????????????????185?????????????????190

Asp?Pro?Glu?His?Ile?Glu?Arg?Gly?Arg?Lys?Leu?Ala?Tyr?Leu?Gly?Leu

195?????????????????200?????????????????205

Glu?Gln?Thr?Ser?Gly?Phe?Ala?Gln?Ala?Glu?Arg?Ala?Ala?Thr?Arg?Trp

210?????????????????215?????????????????220

Trp?Asp?Phe?Glu?Val?Ser?Ser?Phe?Ser?Arg?Arg?Ser?Val?Met?Asn?Asp

225?????????????????230?????????????????235?????????????????240

Val?Leu?Ala?Ala?Ile?Gly?Cys?Val?Gln?Leu?Gly?Arg?Leu?Gly?Glu?Phe

245?????????????????250?????????????????255

Leu?Thr?Arg?Arg?Ala?Glu?Val?Ser?Ala?His?Tyr?Asp?Arg?Glu?Phe?Ala

260?????????????????265?????????????????270

Asp?Leu?Val?Asp?Ile?Pro?Pro?Pro?Leu?Pro?Ala?Gly?His?Arg?Gly?Ser

275?????????????????280?????????????????285

His?Tyr?Phe?Tyr?Trp?Val?Gln?Leu?Pro?Pro?His?Leu?Arg?Asp?Glu?Val

290?????????????????295?????????????????300

Ala?Arg?Asp?Leu?Tyr?Gln?Arg?Gly?Ile?Tyr?Thr?Thr?Tyr?Arg?Tyr?Pro

305?????????????????310?????????????????315?????????????????320

Ser?Leu?His?Arg?Val?Ala?Ala?Phe?Gly?Ser?Thr?Ala?Glu?Leu?Pro?Gly

325?????????????????330?????????????????335

Ala?Asp?His?Ala?Ala?Glu?Arg?Thr?Leu?Cys?Leu?Pro?Met?His?Gln?Gly

340?????????????????345?????????????????350

Leu?Ser?Asp?Ala?Asp?Val?Thr?Ala?Val?Val?Asp?Gly?Leu?Lys?Ala?Ala

355?????????????????360?????????????????365

Leu?Ala?Ala?Arg?Thr?Ala?Gly?Val?Ala?Arg

370?????????????????375

<210>16

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<400>1

Met?Ala?Ser?His?Gly?His?Val?Val?Pro?Thr?Leu?Gly?Val?Ala?Glu?Glu

1???????????????5???????????????????10??????????????????15

Leu?Val?Ala?Arg?Gly?His?Arg?Val?Thr?Tyr?Pro?Ala?Ala?Gly?Asp?Tyr

20??????????????????25??????????????????30

Ala?Thr?Ala?Val?Ala?Glu?Thr?Gly?Ala?Arg?Val?Leu?Pro?Tyr?Glu?Ser

35??????????????????40??????????????????45

Val?Leu?Val?Gly?Arg?Gln?Leu?Thr?Gly?Ala?Leu?Gly?Gly?Gly?Asp?Pro

50??????????????????55??????????????????60

Val?Ala?Asn?Phe?Glu?Leu?Phe?Leu?Ala?Glu?Gly?Ala?Ala?Ile?Leu?Arg

65??????????????????70??????????????????75??????????????????80

Ala?Val?Arg?Ala?Ala?Tyr?Gly?Asp?Arg?Arg?Pro?Asp?Leu?Val?Val?Tyr

85??????????????????90??????????????????95

Asp?Gln?Met?Ala?Asn?Gly?Ile?Gly?Arg?Leu?Ile?Ala?Ala?Glu?Trp?Gly

100?????????????????105?????????????????110

Val?Pro?Val?Val?Gln?Thr?Ile?Pro?Thr?Pro?Val?Tyr?Thr?Asp?Gln?Phe

115?????????????????120?????????????????125

Trp?Ala?Glu?Asp?Asn?Thr?Gly?Lys?Ala?Arg?Gly?Pro?Met?Gly?Arg?Asp

130?????????????????135?????????????????140

Pro?Gly?Ala?Val?Ala?Ala?Ala?His?Ala?Arg?Met?Gln?Asp?Ala?Leu?Gly

145?????????????????150?????????????????155?????????????????160

Arg?His?Gly?Ile?Asp?Met?Pro?Val?Ala?Glu?Tyr?Leu?Ala?Ala?Thr?Ser

165?????????????????170?????????????????175

Glu?Ala?Leu?Asn?Ile?Val?Phe?Leu?Pro?Ser?Ala?Phe?Gln?Gln?Asp?Ala

180?????????????????185?????????????????190

Glu?Lys?Leu?Gly?Glu?Arg?Tyr?Val?Phe?Val?Gly?Pro?Cys?Leu?Pro?Lys

195?????????????????200?????????????????205

Arg?Asp?Phe?Leu?Gly?Glu?Trp?Arg?Pro?Pro?Ala?Ser?Glu?Leu?Pro?Val

210?????????????????215?????????????????220

Val?Leu?Ile?Ser?Leu?Gly?Thr?Val?Tyr?Asn?Glu?Asn?Val?Asp?Phe?Phe

225?????????????????230?????????????????235?????????????????240

Arg?Ser?Cys?Val?Arg?Asp?Phe?Ala?Asp?Gly?Ala?Trp?His?Val?Val?Ile

245?????????????????250?????????????????255

Ser?Leu?Gly?Asp?Gly?Val?Asp?Pro?Ser?Val?Leu?Gly?Glu?Leu?Pro?Pro

260?????????????????265?????????????????270

Asn?Val?Glu?Val?His?Arg?Trp?Val?Ser?His?Ala?Ala?Val?Leu?Glu?His

275?????????????????280?????????????????285

Ala?Ser?Ala?Leu?Val?Thr?His?Gly?Gly?Leu?Gly?Ser?Val?Met?Thr?Gly

290?????????????????295?????????????????300

Leu?His?Trp?Ala?Thr?Pro?Val?Val?Val?Val?Pro?Val?Thr?Pro?Leu?Val

305?????????????????310?????????????????315?????????????????320

Asp?Ile?His?Ala?Arg?Val?Val?Ala?Leu?Gly?Leu?Gly?Thr?Arg?Val?Glu

325?????????????????330?????????????????335

Val?Ala?Asp?Val?Gln?Val?Gly?Arg?Leu?Arg?Glu?Ala?Val?Asp?Gln?Val

340?????????????????345?????????????????350

Ala?Asn?Asp?Thr?Ala?Ile?Arg?Thr?Ala?Val?Ala?Glu?Met?Arg?Glu?His

355?????????????????360?????????????????365

Ile?Arg?His?Ala?Gly?Gly?Ala?Ala?Lys?Ala?Ala?Glu?Glu?Ile?Glu?Ser

370?????????????????375?????????????????380

Tyr?Leu?Gly?Arg?Val?Ala?Ile?Ala

385?????????????????390

<210>16

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<400>1

Met?Ala?Ser?His?Gly?His?Val?Val?Pro?Thr?Leu?Gly?Val?Ala?Glu?Glu

1???????????????5???????????????????10??????????????????15

Leu?Val?Ala?Arg?Gly?His?Arg?Val?Thr?Tyr?Pro?Ala?Ala?Gly?Asp?Tyr

20??????????????????25??????????????????30

Ala?Thr?Ala?Val?Ala?Glu?Thr?Gly?Ala?Arg?Val?Leu?Pro?Tyr?Glu?Ser

35??????????????????40??????????????????45

Val?Leu?Val?Gly?Arg?Gln?Leu?Thr?Gly?Ala?Leu?Gly?Gly?Gly?Asp?Pro

50??????????????????55??????????????????60

Val?Ala?Asn?Phe?Glu?Leu?Phe?Leu?Ala?Glu?Gly?Ala?Ala?Ile?Leu?Arg

65??????????????????70??????????????????75??????????????????80

Ala?Val?Arg?Ala?Ala?Tyr?Gly?Asp?Arg?Arg?Pro?Asp?Leu?Val?Val?Tyr

85??????????????????90??????????????????95

Asp?Gln?Met?Ala?Asn?Gly?Ile?Gly?Arg?Leu?Ile?Ala?Ala?Glu?Trp?Gly

100?????????????????105?????????????????110

Val?Pro?Val?Val?Gln?Thr?Ile?Pro?Thr?Pro?Val?Tyr?Thr?Asp?Gln?Phe

115?????????????????120?????????????????125

Trp?Ala?Glu?Asp?Asn?Thr?Gly?Lys?Ala?Arg?Gly?Pro?Met?Gly?Arg?Asp

130?????????????????135?????????????????140

Pro?Gly?Ala?Val?Ala?Ala?Ala?His?Ala?Arg?Met?Gln?Asp?Ala?Leu?Gly

145?????????????????150?????????????????155?????????????????160

Arg?His?Gly?Ile?Asp?Met?Pro?Val?Ala?Glu?Tyr?Leu?Ala?Ala?Thr?Ser

165?????????????????170?????????????????175

Glu?Ala?Leu?Asn?Ile?Val?Phe?Leu?Pro?Ser?Ala?Phe?Gln?Gln?Asp?Ala

180?????????????????185?????????????????190

Glu?Lys?Leu?Gly?Glu?Arg?Tyr?Val?Phe?Val?Gly?Pro?Cys?Leu?Pro?Lys

195?????????????????200?????????????????205

Arg?Asp?Phe?Leu?Gly?Glu?Trp?Arg?Pro?Pro?Ala?Ser?Glu?Leu?Pro?Val

210?????????????????215?????????????????220

Val?Leu?Ile?Ser?Leu?Gly?Thr?Val?Tyr?Asn?Glu?Asn?Val?Asp?Phe?Phe

225?????????????????230?????????????????235?????????????????240

Arg?Ser?Cys?Val?Arg?Asp?Phe?Ala?Asp?Gly?Ala?Trp?His?Val?Val?Ile

245?????????????????250?????????????????255

Ser?Leu?Gly?Asp?Gly?Val?Asp?Pro?Ser?Val?Leu?Gly?Glu?Leu?Pro?Pro

260?????????????????265?????????????????270

Asn?Val?Glu?Val?His?Arg?Trp?Val?Ser?His?Ala?Ala?Val?Leu?Glu?His

275?????????????????280?????????????????285

Ala?Ser?Ala?Leu?Val?Thr?His?Gly?Gly?Leu?Gly?Ser?Val?Met?Thr?Gly

290?????????????????295?????????????????300

Leu?His?Trp?Ala?Thr?Pro?Val?Val?Val?Val?Pro?Val?Thr?Pro?Leu?Val

305?????????????????310?????????????????315?????????????????320

Asp?Ile?His?Ala?Arg?Val?Val?Ala?Leu?Gly?Leu?Gly?Thr?Arg?Val?Glu

325?????????????????330?????????????????335

Val?Ala?Asp?Val?Gln?Val?Gly?Arg?Leu?Arg?Glu?Ala?Val?Asp?Gln?Val

340?????????????????345?????????????????350

Ala?Asn?Asp?Thr?Ala?Ile?Arg?Thr?Ala?Val?Ala?Glu?Met?Arg?Glu?His

355?????????????????360?????????????????365

Ile?Arg?His?Ala?Gly?Gly?Ala?Ala?Lys?Ala?Ala?Glu?Glu?Ile?Glu?Ser

370?????????????????375?????????????????380

Tyr?Leu?Gly?Arg?Val?Ala?Ile?Ala

385?????????????????390

<210>17

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<400>1

Met?Thr?Arg?Ala?Asp?Ala?Ala?Thr?Tyr?Pro?Phe?Pro?Val?Arg?Cys?Pro

1???????????????5???????????????????10??????????????????15

Phe?Thr?Leu?Pro?Asp?Glu?Leu?Glu?Arg?Leu?Ser?Arg?Glu?Glu?Pro?Val

20??????????????????25??????????????????30

Ala?Pro?Val?Arg?Leu?Pro?Thr?Gly?Ala?Pro?Ala?Trp?Leu?Val?Ser?Gly

35??????????????????40??????????????????45

His?Glu?Gln?Val?Arg?Thr?Val?Leu?Ala?Asp?Glu?Arg?Phe?Ser?Arg?Arg

50??????????????????55??????????????????60

Pro?Ala?Arg?Glu?Arg?Ala?Ala?Lys?Pro?Gly?Gly?Gly?Gly?Phe?Asp?Phe

65??????????????????70??????????????????75??????????????????80

Gly?Leu?Ala?Ile?Ala?Asp?Pro?Ala?Asp?His?Glu?Arg?Trp?Arg?Arg?Leu

85??????????????????90??????????????????95

Val?Gly?Gln?Val?Leu?Asn?Pro?Arg?His?Ala?Glu?Ser?Val?Arg?Pro?Ala

100?????????????????105?????????????????110

Val?Arg?Glu?Leu?Ala?Gly?Ala?Ala?Val?Gly?Arg?Leu?Ala?Asp?Arg?Gly

115?????????????????120?????????????????125

Gly?Pro?Val?Asp?Phe?Met?Ala?Glu?Phe?Ala?Phe?Arg?Leu?Pro?Leu?Asp

130?????????????????135?????????????????140

Val?Leu?Cys?Ala?Leu?Tyr?Ala?Val?Pro?Ala?Asp?Leu?Arg?Pro?Ala?Phe

145?????????????????150?????????????????155?????????????????160

Asp?Ala?Trp?Ala?Ala?Gly?Leu?Arg?Gly?Ala?Ala?Gly?Ser?Met?Glu?Ala

165?????????????????170?????????????????175

Phe?Gly?Ala?Ala?Met?Arg?Thr?Leu?His?Asp?Ala?Ala?Arg?Glu?Leu?Val

180?????????????????185?????????????????190

Ala?Arg?Lys?Pro?Ala?Asp?Gly?Val?Leu?Pro?Ala?Leu?Ala?Glu?Val?Arg

195?????????????????200?????????????????205

Gly?Pro?Asp?Gly?Asp?Arg?Leu?Ser?Glu?Thr?Glu?Leu?Val?Ser?Thr?Val

210?????????????????215?????????????????220

Val?Leu?Leu?Ser?Ile?Ala?Gly?Tyr?Glu?Thr?Gly?Ala?Val?Gln?Phe?Gly

225?????????????????230?????????????????235?????????????????240

Asn?Gly?Leu?Leu?Ala?Leu?Phe?Gln?His?Pro?Asp?Gln?Leu?Ala?Arg?Leu

245?????????????????250?????????????????255

Ala?Ala?Gly?Glu?Val?Asp?Ile?Ala?Ala?Ala?Val?Glu?Glu?Val?Leu?Arg

260?????????????????265?????????????????270

Tyr?Ala?Gln?Ala?Gly?Thr?Gly?Phe?Ala?Gly?Met?Thr?Tyr?Thr?Ser?Ala

275?????????????????280?????????????????285

Asp?Val?Asp?Leu?Gly?Gly?Thr?Thr?Ile?Pro?Ala?His?Ala?Gln?Val?Leu

290?????????????????295?????????????????300

Ile?Ser?Leu?Asp?Ala?Ala?Gly?Arg?Asp?Pro?Gly?Arg?Val?Glu?Arg?Pro

305?????????????????310?????????????????315?????????????????320

His?Glu?Phe?Asp?Leu?Ala?Arg?Gly?Ala?Ala?Gly?Gly?His?Leu?Ser?Phe

325?????????????????330?????????????????335

Gly?Ser?Gly?Arg?His?Tyr?Cys?Leu?Gly?Ala?Pro?Leu?Ala?Arg?Val?Glu

340?????????????????345?????????????????350

Leu?Gln?Glu?Gly?Phe?Ala?Ala?Leu?Val?Arg?Gly?Leu?Pro?Gly?Leu?Arg

355?????????????????360?????????????????365

Ala?Ala?Val?Arg?Pro?Asp?Glu?Val?Val?Met?Gly?Arg?Thr?Met?Phe?Ser

370?????????????????375?????????????????380

Phe?Tyr?Pro?Ala?Glu?Leu?Pro?Thr?Thr?Trp?Ala?Phe?Glu?Arg?Thr?Asp

385?????????????????390?????????????????395?????????????????400

Ala?Arg

<210>18

<211>370

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ala?Asp?Thr?Gln?Ala?Pro?Pro?His?Gly?Leu?Leu?Trp?Arg?Ala?Glu

1???????????????5???????????????????10??????????????????15

Thr?Asn?Gln?Trp?Val?Val?Thr?Thr?His?Glu?Val?Ala?Asp?Thr?Val?Leu

20??????????????????25??????????????????30

Arg?Asp?Pro?His?Ile?Gly?Thr?Ala?Leu?Asp?Pro?Asp?Arg?Ala?Ala?Val

35??????????????????40??????????????????45

Pro?Thr?Pro?Gly?Ala?Asp?Asp?Val?Pro?Thr?Val?Ser?Gln?Phe?Phe?Glu

50??????????????????55??????????????????60

Leu?Trp?Tyr?Arg?Arg?Gly?Ala?Asn?His?Pro?Thr?Phe?Lys?His?Arg?Leu

65??????????????????70??????????????????75??????????????????80

Arg?Ala?Ala?Tyr?Ser?Ala?Ala?Ala?Val?Ala?Ala?Phe?Ala?Pro?Ala?Phe

85??????????????????90??????????????????95

Glu?Ala?Arg?Ala?Arg?Glu?Leu?Ala?Glu?Ala?Leu?Pro?Ala?Glu?Gly?Asp

100?????????????????105?????????????????110

Leu?Val?Ala?Asp?Phe?Ile?Ala?Pro?Phe?Ala?Leu?Asp?Ser?Thr?Phe?Arg

115?????????????????120?????????????????125

Phe?Met?Gly?Phe?Pro?Ala?Arg?His?Gln?Ala?Asn?Leu?Ala?Lys?Ser?Tyr

130?????????????????135?????????????????140

Arg?Val?Leu?Met?Phe?Val?Ile?Lys?Gln?Arg?Phe?Leu?Gly?Val?Leu?Asp

145?????????????????150?????????????????155?????????????????160

Leu?Pro?Gln?Arg?Gln?Arg?Ala?Ala?Phe?Gly?Ser?Val?Leu?Ala?Phe?Leu

165?????????????????170?????????????????175

Arg?Asp?Ala?Thr?Ala?Glu?Ala?Leu?Ala?Ala?Pro?Asp?Pro?Thr?Pro?Leu

180?????????????????185?????????????????190

Ala?Ala?Ala?Phe?Leu?Ala?Gln?Ala?Glu?Ala?Asp?Gly?Glu?Ile?Pro?Trp

195?????????????????200?????????????????205

Ala?Asp?Val?Ala?Thr?Val?Gly?Gln?Leu?Leu?Ala?Ala?Gly?Val?Pro?Gln

210?????????????????215?????????????????220

Val?Glu?Thr?Gly?Ile?Ala?Val?Ala?Ala?His?Ala?Leu?Leu?Thr?Arg?Pro

225?????????????????230?????????????????235?????????????????240

Glu?Ala?Val?Gly?Ala?Asp?Leu?Ala?Gly?Val?Ala?Glu?Glu?Ala?Met?Arg

245?????????????????250?????????????????255

Leu?Ala?Pro?Pro?Phe?Leu?Gly?Ile?Phe?Gly?Trp?Val?Thr?Glu?Pro?Cys

260?????????????????265?????????????????270

Asp?Cys?Leu?Gly?Val?Arg?Leu?Glu?Pro?Arg?Thr?Ala?Ile?Val?Val?Asp

275?????????????????280?????????????????285

Ile?Pro?Ala?Val?Asn?Ala?Asp?Pro?Ala?Lys?Val?Ala?Asp?Pro?Ala?Ala

290?????????????????295?????????????????300

Phe?Cys?Pro?Gly?Arg?Ser?Arg?Ala?Glu?Asn?Ile?Thr?Phe?Gly?Lys?Gly

305?????????????????310?????????????????315?????????????????320

Ala?His?Tyr?Cys?Leu?Gly?Ala?Ala?Ser?Ala?Arg?Ala?Gln?Val?Val?Ala

325?????????????????330?????????????????335

Ala?Leu?Arg?Gly?Leu?Leu?Ala?Ala?Arg?Pro?Asp?Leu?Asp?Leu?Gly?Ala

340?????????????????345?????????????????350

Leu?Gln?Arg?Ala?Asp?Asp?Gly?Phe?Ala?Gln?Ser?Ile?Thr?Ala?Leu?His

355?????????????????360?????????????????365

Tyr?Arg

370

<210>19

<211>412

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Thr?Thr?Thr?Ile?Pro?Val?Glu?Pro?Val?Asp?Leu?Ala?Asp?Ala?Ala

1???????????????5???????????????????10??????????????????15

Leu?Val?Glu?Asn?Pro?Tyr?Pro?His?Tyr?Ala?Arg?Leu?Arg?Gly?Ala?Gly

20??????????????????25??????????????????30

Ala?Pro?Val?Arg?Ser?Ser?Val?Trp?Asp?Cys?Trp?Phe?Ala?Ala?Thr?His

35??????????????????40??????????????????45

Ala?Gln?Cys?His?Ala?Val?Phe?Gly?Asp?Ser?Arg?Phe?Ser?Ala?Val?Gly

50??????????????????55??????????????????60

Gln?Pro?Met?Leu?Arg?Gly?Leu?Gln?Ala?Ala?Val?Val?Ser?Gly?Ala?Arg

65??????????????????70??????????????????75??????????????????80

Ser?Tyr?Ala?Leu?Pro?Glu?Pro?Pro?Pro?Glu?Pro?Asp?Ala?Ser?Ala?His

85??????????????????90??????????????????95

Arg?Ala?Gln?Gly?Arg?Arg?Thr?Thr?Gly?Arg?Ala?Leu?Ser?Thr?Gly?Tyr

100?????????????????105?????????????????110

Val?Asp?Gly?Leu?Trp?Pro?Gly?Phe?Ala?Ala?Ala?Cys?Arg?Glu?Leu?Ala

115?????????????????120?????????????????125

Ala?Asp?Leu?Ala?Ala?Arg?Pro?Gly?Pro?Val?Asp?Val?Val?Ala?Asp?Tyr

130?????????????????135?????????????????140

Ala?Ile?Pro?Leu?Ala?Thr?Arg?Leu?Leu?Ala?Asp?Leu?Met?Ala?Ile?Ala

145?????????????????150?????????????????155?????????????????160

Asp?Ala?Asp?Leu?Pro?Ala?Phe?Arg?Ala?Trp?Ala?Glu?Ser?Gly?Tyr?Gly

165?????????????????170?????????????????175

Pro?Pro?Ala?Asp?Ala?Ala?Asp?Gln?Arg?Arg?Ile?Val?Arg?Gly?Ile?Arg

180?????????????????185?????????????????190

Glu?Leu?Leu?Ala?Arg?Ser?Ala?Val?Gly?Arg?Leu?Arg?Glu?Pro?Thr?Gln

195?????????????????200?????????????????205

Asp?Phe?Ile?Gly?His?Leu?Val?Ala?Asn?Pro?Gly?Thr?Leu?Thr?Gly?Gly

210?????????????????215?????????????????220

Gly?Gly?Val?Gly?Glu?His?Leu?Glu?Phe?Val?Leu?Gly?Thr?Gly?Leu?Met

225?????????????????230?????????????????235?????????????????240

Ile?Ser?Leu?Val?Thr?His?Gln?Gly?Leu?Val?Leu?Ser?Phe?Gly?Thr?Leu

245?????????????????250?????????????????255

Val?Asp?Ala?Leu?Ala?Arg?His?Pro?Gly?Gln?Tyr?Ala?Arg?Val?Arg?Ala

260?????????????????265?????????????????270

Asp?Arg?Ala?Leu?Val?Pro?Gly?Ala?Val?Glu?Glu?Gly?Leu?Arg?Tyr?Asp

275?????????????????280?????????????????285

Pro?Ser?Thr?Gln?Ala?Leu?Gly?Arg?Leu?Ala?Arg?Ala?Asp?Val?Val?Ile

290?????????????????295?????????????????300

Asp?Gly?Thr?Pro?Ile?Pro?Ala?Gly?Gly?Leu?Val?Leu?Cys?Leu?Val?Gly

305?????????????????310?????????????????315?????????????????320

Ser?Ala?Asn?Arg?Asp?Pro?Ala?Gln?Trp?Pro?Asp?Ala?Asp?Thr?Phe?Asp

325?????????????????330?????????????????335

Val?Gly?Arg?Asp?Thr?Arg?Ala?Ala?Ala?Arg?His?Leu?Thr?Phe?Gly?Trp

340?????????????????345?????????????????350

Gly?Ala?Thr?Ser?Cys?Leu?Gly?Ala?Ala?Met?Ser?Arg?Gln?Ala?Met?Ser

355?????????????????360?????????????????365

His?Met?Leu?Ala?Ala?Leu?Val?Asp?Ala?Ala?Asp?Ala?Val?Thr?Pro?Ser

370?????????????????375?????????????????380

Ser?Gly?Ala?Val?Arg?Phe?Pro?Glu?Phe?Met?Thr?Arg?Gly?Tyr?Thr?Ala

385?????????????????390?????????????????395?????????????????400

Leu?Pro?Val?His?Leu?Thr?Pro?Ala?Arg?Ser?Asp?Gly

405?????????????????410

<210>20

<211>380

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Val?Ala?Leu?Ala?Ala?Thr?Ala?Leu?Pro?Asp?Gly?Leu?Arg?Trp

1???????????????5???????????????????10??????????????????15

Asp?Ala?Gly?Arg?Asn?Arg?Leu?Lys?Val?Leu?Ser?Pro?Ala?Leu?Ala?Asp

20??????????????????25??????????????????30

Val?Val?Leu?Arg?Asp?Pro?His?Ile?Ile?Thr?Gly?Val?Asp?Arg?Ser?Arg

35??????????????????40??????????????????45

Ala?Gly?Met?Ala?Thr?Ala?Met?Pro?Glu?Glu?Asn?Ala?Thr?Pro?Ser?Ile

50??????????????????55??????????????????60

Thr?Gln?Phe?Phe?Glu?Leu?Trp?Tyr?Thr?Val?Ser?Asp?Asn?Tyr?Ala?Pro

65??????????????????70??????????????????75??????????????????80

Phe?Asn?Thr?Glu?Leu?Arg?Lys?Val?Phe?Thr?Ile?Arg?Ser?Ala?Asp?Ser

85??????????????????90??????????????????95

Tyr?Val?Asp?Met?Phe?Glu?Arg?Met?Ala?Ala?Glu?Arg?Ala?Ala?Ala?Leu

100?????????????????105?????????????????110

Pro?Ala?Asp?Gly?Asp?Leu?Ala?Arg?Asp?Tyr?Phe?Ser?Pro?Phe?Phe?Met

115?????????????????120?????????????????125

Asp?Ser?Thr?Phe?Ala?Met?Ile?Gly?Val?Pro?Glu?Ala?Asp?Trp?Pro?Asn

130?????????????????135?????????????????140

Leu?Thr?Lys?Val?Ala?Lys?Leu?Val?Ile?His?Leu?Phe?Lys?Gln?Gln?Leu

145?????????????????150?????????????????155?????????????????160

Leu?Gly?Val?Thr?Asp?Tyr?Gly?Ala?Arg?Glu?Gln?Ala?Ala?Phe?Ala?Ala

165?????????????????170?????????????????175

Val?Met?Arg?Tyr?Leu?Lys?Asp?Leu?Thr?Asp?Arg?Leu?Leu?Ala?Glu?Ala

180?????????????????185?????????????????190

Asp?Ser?Pro?Phe?Val?Asp?Ala?Ala?Arg?Arg?Leu?Ser?Ala?Met?Asp?Arg

195?????????????????200?????????????????205

Ser?Thr?Trp?Pro?Ile?Ala?Ala?Leu?Ile?Gly?Gln?Leu?Leu?Met?Ala?Gly

210?????????????????215?????????????????220

Ile?Glu?Pro?Met?Ile?Val?Gly?Gly?Ala?Ile?Ala?Ser?Arg?Met?Val?Trp

225?????????????????230?????????????????235?????????????????240

Ser?Asp?Pro?Glu?Leu?Pro?Gly?Leu?Leu?Arg?Ala?Gly?Glu?Val?Asp?Ala

245?????????????????250?????????????????255

Gly?Glu?Val?Ala?Glu?Glu?Cys?Met?Arg?Gln?Ser?Pro?Pro?Phe?Gly?Asn

260?????????????????265?????????????????270

Val?Phe?Arg?Phe?Val?Ala?Glu?Pro?Cys?Ser?Cys?Leu?Gly?Val?Pro?Leu

275?????????????????280?????????????????285

Glu?Pro?Gly?Thr?Ile?Val?Ala?Ile?Asp?Thr?Glu?Ala?Val?Asn?Leu?Ala

290?????????????????295?????????????????300

Glu?Ser?Gly?Pro?Thr?Ala?Pro?Val?Arg?Gly?Cys?Pro?Val?Arg?Pro?Thr

305?????????????????310?????????????????315?????????????????320

Ala?Val?Leu?Thr?Phe?Gly?Arg?Gly?Gly?His?Tyr?Cys?Leu?Gly?Ala?Asn

325?????????????????330?????????????????335

Thr?Ala?Arg?Arg?Gln?Val?Ala?Ala?Ala?Leu?Arg?Ala?Leu?Val?Thr?Ala

340?????????????????345?????????????????350

Arg?Pro?Gly?Leu?Arg?Ile?Asp?Pro?Ala?Ala?Val?Arg?Ile?Asp?Thr?His

355?????????????????360?????????????????365

Asn?Asn?Leu?Lys?Glu?Val?Arg?Ala?Leu?Pro?Tyr?Ser

370?????????????????375?????????????????380

<210>21

<211>426

<212>PRT

<213>Nocardia?sp.WW-12651

<400>l

Val?Thr?Thr?Gln?Asp?Gly?Gln?Asp?Ser?Gln?Asp?Gly?Gln?Asp?Ser?Gln

l???????????????5???????????????????10??????????????????15

Asp?Ser?Thr?Val?Gly?Leu?Thr?Gly?Lys?Thr?Tyr?Pro?Phe?Glu?Arg?Lys

20??????????????????25??????????????????30

Cys?Pro?Phe?Ala?Met?Pro?Glu?Glu?Phe?Ala?Trp?Ala?Arg?Glu?Asn?Glu

35??????????????????40??????????????????45

Pro?Val?Ala?Gln?Val?Lys?Leu?Gln?Ser?Gly?Asp?Leu?Ala?Trp?Leu?Ile

50??????????????????55??????????????????60

Thr?Lys?Tyr?Gly?Asp?Val?Lys?Ala?Ala?Leu?Gly?Asp?Asp?Arg?Phe?Ser

65??????????????????70??????????????????75??????????????????80

Arg?Thr?Ile?Asn?Arg?Glu?Gly?Ala?Ala?Arg?Val?Asp?Thr?Gly?Phe?Ser

85??????????????????90??????????????????95

Ala?Asp?Arg?Ser?Ser?Pro?Val?Phe?Thr?Phe?Gly?Gly?Ser?Ile?Ser?Gln

100?????????????????105?????????????????110

Pro?Pro?Gly?His?Thr?Arg?Trp?Arg?Arg?Ile?Val?Asn?Lys?Ala?Phe?Thr

115?????????????????120?????????????????125

Gln?Arg?Gln?Ala?Asp?Ala?Met?Arg?Ala?Glu?Ile?Ala?Arg?His?Thr?Glu

130?????????????????135?????????????????140

Glu?Val?Leu?Asp?Glu?Leu?Glu?Ala?Arg?Gly?Pro?Ser?Phe?Asp?Leu?Met

145?????????????????150?????????????????155?????????????????160

Ala?Asp?Tyr?Ala?Tyr?Lys?Leu?Pro?Ile?Arg?Ile?Ile?Cys?Asp?Leu?Leu

165?????????????????170?????????????????175

Gly?Ile?Pro?Asn?Glu?Ser?Arg?Pro?Glu?Phe?Thr?Glu?Leu?Ala?Ala?Lys

180?????????????????185?????????????????190

Leu?Thr?Arg?Arg?Asp?Met?Gln?Ser?Gly?Phe?Ala?Ala?Phe?Gly?Glu?Ala

195?????????????????200?????????????????205

Leu?Gln?Gly?Ile?Gly?Arg?Tyr?Ala?Val?Gly?Leu?Ile?Val?Arg?Lys?Arg

210?????????????????215?????????????????220

Lys?Asn?Leu?Gly?Asp?Asp?Leu?Leu?Ser?Thr?Leu?Ile?Gln?Leu?Arg?Asp

225?????????????????230?????????????????235?????????????????240

Asp?Asp?Glu?Thr?Gln?Leu?Ser?Asn?Glu?Glu?Leu?Val?Ser?Thr?Val?Ile

245?????????????????250?????????????????255

Leu?Leu?Leu?Met?Ala?Gly?Tyr?Glu?Ser?Thr?Ala?Val?Gln?Phe?Gly?Asn

260?????????????????265?????????????????270

Ala?Phe?Tyr?Ala?Leu?Phe?Arg?His?Pro?Glu?Gln?Leu?Ala?Leu?Leu?Arg

275?????????????????280?????????????????285

Glu?Arg?Pro?Glu?Leu?Ile?Gly?Gly?Ala?Val?Glu?Glu?Ile?Leu?Arg?Trp

290?????????????????295?????????????????300

Ala?Gln?Met?Gly?Thr?Gly?Phe?Ala?Val?Ala?Lys?Phe?Ala?Thr?Glu?Asp

305?????????????????310?????????????????315?????????????????320

Ile?Pro?Met?Pro?Gly?Ala?Thr?Ile?Pro?Ala?Gly?Gly?Thr?Val?Phe?Val

325?????????????????330?????????????????335

Ser?Leu?Gly?Ser?Gly?Asn?Arg?Asp?Gln?Glu?Val?Phe?Gly?Pro?Asp?Ala

340?????????????????345?????????????????350

Glu?Lys?Phe?Asp?Val?Thr?Arg?Val?Ala?Pro?Ala?Arg?Gln?Leu?Ala?Phe

355?????????????????360?????????????????365

Gly?Ser?Gly?Pro?His?Phe?Cys?Leu?Gly?Ala?Ala?Leu?Ala?Arg?Ala?Glu

370?????????????????375?????????????????380

Met?Gln?Glu?Gly?Ile?Leu?Arg?Leu?Leu?Thr?Arg?Phe?Pro?Asn?Leu?Arg

385?????????????????390?????????????????395?????????????????400

Tyr?Asp?Gly?Asp?Leu?Asp?Ala?Val?Pro?Leu?Ala?Ser?Asn?Leu?Phe?Thr

405?????????????????410?????????????????415

Tyr?Tyr?Pro?Arg?Glu?Leu?Pro?Val?Ile?Ala

420?????????????????425

<210>22

<211>207

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Glu?Thr?Ala?Lys?Thr?Ser?Arg?Thr?Ala?Arg?Ser?Ser?Lys?Leu

1???????????????5???????????????????10??????????????????15

Val?Ser?Lys?Val?Tyr?Asn?Ala?Ala?Tyr?Lys?Val?Gly?Phe?Ser?Pro?Trp

20??????????????????25??????????????????30

Asp?Leu?Gly?Pro?Pro?Met?Pro?Glu?Leu?Val?Ala?Leu?Ile?Glu?Gly?Pro

35??????????????????40??????????????????45

Asp?Arg?Leu?Ala?Pro?Gly?Arg?Ala?Leu?Asp?Leu?Gly?Cys?Gly?Thr?Gly

50??????????????????55??????????????????60

Gly?Lys?Ser?Ile?Tyr?Leu?Ala?Glu?His?Gly?Trp?Ser?Val?Thr?Gly?Ala

65??????????????????70??????????????????75??????????????????80

Asp?Ile?Ala?Pro?Glu?Ala?Leu?Arg?Arg?Ala?Arg?Lys?Arg?Ala?Gly?Asp

85??????????????????90??????????????????95

Ala?Gly?Val?Asp?Val?Glu?Phe?Val?Glu?Cys?Asp?Leu?Val?Asp?Ile?Pro

100?????????????????105?????????????????110

Ala?Gly?Ala?Leu?Gly?Gly?Pro?Tyr?Asp?Phe?Leu?Leu?Asp?Phe?Gly?Cys

115?????????????????120?????????????????125

Ser?His?Ser?Leu?Arg?Asp?Glu?Ala?Lys?Ala?Arg?Tyr?Ala?Glu?Gly?Val

130?????????????????135?????????????????140

Ala?Gly?Val?Ala?Ala?Pro?Gly?Ala?Thr?Leu?Tyr?Leu?Tyr?Ala?Phe?Thr

145?????????????????150?????????????????155?????????????????160

Lys?Gly?Pro?Leu?Ser?Val?Arg?Pro?Glu?Glu?Ile?Asp?Thr?Ala?Phe?Ala

165?????????????????170?????????????????175

Pro?His?Trp?Asp?Leu?Val?Ser?Ala?Val?Pro?Gly?Ser?Val?Arg?Arg?Thr

180?????????????????185?????????????????190

Pro?Asp?Ala?Gly?Pro?Met?Trp?Tyr?Arg?Met?Thr?Arg?Arg?Ala?Ala

195?????????????????200?????????????????205

<210>23

<211>261

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Asp?Ser?Ser?Phe?Gly?Val?Gly?Leu?Tyr?Gly?Glu?Gln?Asp?Arg?Asp

1???????????????5???????????????????10??????????????????15

Gly?Leu?Pro?Ala?Gln?Ala?Leu?Ala?Ala?Ser?Leu?Gly?Cys?Gly?Asn?Pro

20??????????????????25??????????????????30

Thr?Ala?Val?Ala?Glu?Leu?Arg?Ala?Gly?Glu?Arg?Val?Leu?Asp?Leu?Gly

35??????????????????40??????????????????45

Ser?Gly?Gly?Gly?Ile?Asp?Val?Leu?Leu?Ser?Ala?Arg?Arg?Val?Gly?Pro

50??????????????????55??????????????????60

Thr?Gly?Lys?Ala?Tyr?Gly?Val?Asp?Met?Thr?Asp?Glu?Met?Leu?Ala?Leu

65??????????????????70??????????????????75??????????????????80

Ala?Leu?Ala?Asn?Lys?Ala?Ser?Ala?Gly?Ala?Asp?Asn?Val?Glu?Phe?Leu

85??????????????????90??????????????????95

Lys?Gly?Thr?Ile?Glu?Ala?Leu?Pro?Leu?Pro?Ala?Gly?Thr?Ile?Asp?Val

100?????????????????105?????????????????110

Val?Ile?Ser?Asn?Cys?Val?Ile?Asn?Leu?Ser?Val?Asp?Lys?Pro?Ala?Val

115?????????????????120?????????????????125

Phe?Ala?Glu?Met?Phe?Arg?Val?Leu?Ala?Pro?Gly?Gly?Arg?Ile?Gly?Val

130?????????????????135?????????????????140

Ser?Asp?Val?Val?Ala?Glu?Asp?Ala?Leu?Ser?Ala?Thr?Glu?Arg?Ala?Glu

145?????????????????150?????????????????155?????????????????160

Arg?Gly?Ser?Tyr?Val?Glu?Cys?Ile?Ala?Gly?Ala?Leu?Thr?Phe?Ala?Glu

165?????????????????170?????????????????175

Tyr?Arg?Arg?Gly?Leu?Glu?Arg?Ala?Gly?Phe?Ala?Asp?Val?Asp?Ile?Thr

180?????????????????185?????????????????190

Ala?Thr?His?Gln?Val?Ala?Asp?Gly?Met?His?Ser?Ala?Ile?Val?Arg?Ala

195?????????????????200?????????????????205

Val?Lys?Pro?Ala?Thr?Gly?Pro?Val?Ala?Glu?Pro?Ala?Ala?Val?Ala?Ala

210?????????????????215?????????????????220

Ser?Gly?Ser?Cys?Cys?Gly?Val?Ser?Ala?Cys?Cys?Thr?Pro?Ala?Glu?Ser

225?????????????????230?????????????????235?????????????????240

Ala?Leu?Asp?Arg?Ser?Ser?Thr?Val?Ala?Glu?Ala?Lys?Ala?Ala?Ser?Gly

245?????????????????250?????????????????255

Cys?Gly?Cys?Gln?Ser

260

<210>24

<211>174

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Thr?Thr?His?Ala?Asn?His?Pro?Ser?His?Glu?Ala?Ala?Pro?Glu?Gly

1???????????????5???????????????????10??????????????????15

Val?Gly?Phe?Asp?Asp?Ile?Pro?Asp?Met?Pro?Asn?Phe?Ala?Val?Leu?Leu

20??????????????????25??????????????????30

Val?Ser?Asp?Leu?Glu?Lys?Ser?Leu?Gln?Trp?Tyr?Val?Asp?Gly?Leu?Gly

35??????????????????40??????????????????45

Phe?Trp?Ile?Glu?Lys?Lys?Leu?Thr?Gly?Pro?Asp?Gly?Gln?Ile?Ala?Val

50??????????????????55??????????????????60

Ile?His?Leu?Arg?Arg?Ala?Gln?Tyr?Arg?Asp?Met?Leu?Leu?Arg?Pro?Ala

65??????????????????70??????????????????75??????????????????80

Arg?Glu?Pro?Leu?Asp?Gly?Pro?Leu?Gly?Arg?Gly?Val?Arg?Ile?Ser?Phe

85??????????????????90??????????????????95

Thr?Leu?Asn?Ala?Glu?Thr?Glu?Ala?Ser?Met?Arg?Glu?Ile?Ala?Ala?Arg

100?????????????????105?????????????????110

Ala?Gly?Ala?Leu?Pro?Gln?Gly?Thr?Val?Asn?Gly?Pro?Leu?Ala?Thr?Pro

115?????????????????120?????????????????125

Trp?Asn?Thr?Val?Asp?Val?Glu?Ala?Thr?Asp?Pro?Asp?Gly?Tyr?Val?Val

130?????????????????135?????????????????140

Val?Leu?Thr?Thr?Val?Ala?Asp?Arg?Ala?Arg?Thr?Trp?Ser?Glu?Leu?Lys

145?????????????????150?????????????????155?????????????????160

Lys?Ser?Val?Leu?Ala?Asp?Asp?Thr?Pro?Val?Gln?Leu?Asp?Ser

165?????????????????170

<210>25

<211>169

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Phe?Arg?Arg?Trp?His?Gly?Gly?Pro?Gly?Ala?Asp?Gly?Arg?Asn?Thr

1???????????????5???????????????????10??????????????????15

Pro?Val?Thr?Thr?Arg?Pro?Arg?Ile?Thr?Ala?Ser?Ala?Leu?Thr?Leu?Ala

20??????????????????25??????????????????30

Gly?Ala?Leu?Val?Leu?Ser?Ala?Cys?Gly?Ser?Asp?Asp?Asn?Arg?Asp?Thr

35??????????????????40??????????????????45

Ile?Lys?Trp?Thr?Leu?Asp?Lys?Gly?Asn?Val?Pro?Val?Pro?Thr?Ala?Thr

50??????????????????55??????????????????60

Ile?Pro?Ile?Asp?Cys?Gly?Gly?Thr?Arg?Ala?Leu?Thr?Gly?Glu?Gly?Ser

65??????????????????70??????????????????75??????????????????80

Thr?Ala?Gln?Lys?Gly?Ala?Met?Asp?Val?Phe?Val?Ala?Ala?Tyr?Thr?Gln

85??????????????????90??????????????????95

Gln?Cys?Pro?Gly?Gln?Gln?Met?Ala?Tyr?Thr?Ala?Ser?Gly?Ser?Gly?Ala

100?????????????????105?????????????????110

Gly?Val?Lys?Gln?Phe?Leu?Ala?Gly?Leu?Val?Asp?Ile?Gly?Gly?Ser?Asp

115?????????????????120?????????????????125

Ser?Ala?Leu?Lys?Pro?Glu?Arg?Gly?Glu?Val?Thr?Asp?Ala?Ala?Ala?Arg

130?????????????????135?????????????????140

Cys?Gly?Gly?Asn?Pro?Ala?Trp?Asn?Leu?Pro?Leu?Val?Phe?Gly?Pro?Val

145?????????????????150?????????????????155?????????????????160

Ala?Val?Val?Tyr?Gln?Ile?Arg?Tyr?Leu

165

<210>26

<211>327

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Ala?Asn?Thr?Val?Val?Pro?Leu?Asp?Ala?Ile?Ile?Ala?Glu?Leu?Trp?Gly

65??????????????????70??????????????????75??????????????????80

Asp?Thr?Thr?Pro?Arg?Ser?Ala?Arg?Ala?Val?Val?Gln?Thr?Tyr?Val?Met

85??????????????????90??????????????????95

Gln?Leu?Arg?Lys?Gln?Ala?Ala?Lys?Val?Leu?Ala?Gly?Arg?Val?Asp?Ala

100?????????????????105?????????????????110

Pro?Glu?Ser?Val?Ala?Arg?Glu?Leu?Val?Arg?Thr?Gln?Pro?Gly?Gly?Tyr

115?????????????????120?????????????????125

Val?Leu?Ser?Ala?Asp?Glu?Pro?Ser?Val?Asp?Ala?Trp?Ala?Phe?Glu?Arg

130?????????????????135?????????????????140

Leu?Thr?Thr?Ala?Gly?His?Arg?Glu?Arg?Glu?Ser?Gly?Asp?Leu?Val?Ala

145?????????????????150?????????????????155?????????????????160

Ala?Ser?Arg?Ser?Phe?Ser?Asp?Ala?Leu?Ala?Trp?Trp?Arg?Gly?Gly?Pro

165?????????????????170?????????????????175

Leu?Leu?Asp?Val?Gln?Thr?Gly?Ala?Val?Leu?Asn?Ser?Tyr?Ala?Lys?Arg

180?????????????????185?????????????????190

Leu?Gln?Glu?Ala?His?Leu?Asn?Ala?Leu?Asp?Arg?Arg?Ile?Glu?Val?Asp

195?????????????????200?????????????????205

Leu?Arg?Leu?Gly?Arg?His?Tyr?Glu?Leu?Leu?Gly?Glu?Leu?Thr?Ala?Leu

210?????????????????215?????????????????220

Val?Asn?Arg?Tyr?Pro?Thr?His?Glu?Gly?Leu?Cys?Ala?His?Leu?Met?Leu

225?????????????????230?????????????????235?????????????????240

Ala?Leu?Tyr?Arg?Ser?Gly?Arg?Arg?Ser?Glu?Ala?Leu?Glu?Val?Tyr?Arg

245?????????????????250?????????????????255

Asp?Val?Arg?Ala?Arg?Met?Ile?Ala?Glu?Leu?Ala?Leu?Glu?Pro?Ser?Pro

260?????????????????265?????????????????270

Ala?Leu?Arg?Arg?Leu?His?Arg?Ser?Met?Leu?Val?Ser?Asp?Arg?Ala?Pro

275?????????????????280?????????????????285

Thr?Asp?Leu?Thr?Asp?Thr?Trp?Gln?Ala?Thr?Val?Val?Pro?Pro?Arg?Lys

290?????????????????295?????????????????300

Pro?Ala?Gly?Pro?Ile?Pro?Ala?Asp?Leu?Ala?Ala?Thr?Ser?Trp?Asp?Ile

305?????????????????310?????????????????315?????????????????320

His?Pro?Ala?Ile?Ala?Ser?Asn

325

<210>27

<211>141

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Arg?Thr?Asp?Pro?Phe?Arg?Glu?Leu?Asp?Arg?Leu?Thr?Gln?Gln?Val

1???????????????5???????????????????10??????????????????15

Phe?Gly?Thr?Trp?Thr?Arg?Pro?Ala?Ala?Met?Pro?Met?Asp?Ala?Tyr?Arg

20??????????????????25??????????????????30

Gln?Gly?Asp?Glu?Phe?Val?Val?Val?Phe?Asp?Leu?Pro?Gly?Val?Thr?Ser

35??????????????????40??????????????????45

Glu?Ala?Ile?Asp?Leu?Asp?Ile?Glu?Arg?Asn?Val?Leu?Thr?Val?Lys?Ala

50??????????????????55??????????????????60

Glu?Arg?Arg?Pro?Thr?Ala?Val?Gly?Glu?Gly?Ala?Glu?Thr?Gln?Ile?Ala

65??????????????????70??????????????????75??????????????????80

Glu?Arg?Pro?His?Gly?Val?Phe?Ser?Arg?Gln?Leu?Phe?Leu?Gly?Asp?Gly

85??????????????????90??????????????????95

Leu?Asp?Thr?Asp?Arg?Ile?Gln?Ala?Ala?Tyr?Glu?Asn?Gly?Val?Leu?Thr

100?????????????????105?????????????????110

Leu?Arg?Ile?Pro?Val?Ala?Glu?Arg?Ala?Lys?Pro?Arg?Lys?Ile?Ser?Val

115?????????????????120?????????????????125

Ala?Gly?Ala?Asp?Pro?Ala?Glu?Pro?Lys?Gln?Ile?Asp?Ala

130?????????????????135?????????????????140

<210>28

<211>202

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Glu?Tyr?Gln?Glu?Ala?Arg?Asp?Asp?Leu?Ser?Pro?Arg?Tyr?Gly?Asp

1???????????????5???????????????????10??????????????????15

Val?Pro?Ser?Met?Gln?Leu?Val?Glu?Asp?Val?Ala?Arg?Gly?Glu?Ala?Asp

20??????????????????25??????????????????30

Pro?Ala?His?Val?Leu?Ser?Ala?Leu?Val?Leu?Val?Arg?His?Leu?Arg?Ala

35??????????????????40??????????????????45

His?Leu?Gly?Glu?Leu?Glu?Pro?Gln?Leu?Ile?Ala?Ala?Ala?Arg?Glu?Arg

50??????????????????55??????????????????60

Gly?Val?Ser?Trp?Ala?Arg?Leu?Ala?Pro?Ala?Leu?Gly?Val?Ala?Ser?Arg

65??????????????????70??????????????????75??????????????????80

Gln?Ala?Ala?Glu?Arg?Arg?Tyr?Leu?Arg?Leu?Arg?Pro?Asp?Asp?Asp?His

85??????????????????90??????????????????95

Ala?Thr?Gly?Glu?Glu?Arg?Val?Arg?Ala?Glu?Arg?Asp?Arg?Arg?Ala?Gly

100?????????????????105?????????????????110

Asp?Arg?Ala?Val?Thr?Ala?Trp?Ala?Ala?Arg?Asn?Ser?Ala?Ala?Leu?Arg

115?????????????????120?????????????????125

Gly?Leu?Ala?Gly?Gln?Val?Ala?Gly?Leu?Pro?His?Leu?Thr?Gly?Asp?Ala

130?????????????????135?????????????????140

Arg?Arg?Thr?Ala?Asp?Asp?Val?His?Thr?Ala?Leu?Gly?Gly?Asp?Arg?Ala

145?????????????????150?????????????????155?????????????????160

Ser?Asp?Leu?Leu?Ala?Pro?Leu?His?Asp?Ala?Ala?Pro?His?Leu?Arg?Ala

165?????????????????170?????????????????175

Ala?His?Pro?Gly?Leu?Ala?Asp?Arg?Ile?Asp?Ala?Val?Thr?Ala?Glu?Thr

180?????????????????185?????????????????190

Thr?Arg?Leu?Arg?His?Ala?Ser?Arg?Asp?Arg

195?????????????????200

<210>29

<211>378

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Asp?Glu?Val?Leu?Leu?Arg?Ser?Leu?Thr?Pro?Ser?Val?Ile?Gly?Ile

1???????????????5???????????????????10??????????????????15

Leu?Gly?Arg?Arg?Gly?Ala?Asp?Phe?Ala?Ala?Ala?Glu?Asp?Ala?Val?Gln

20??????????????????25??????????????????30

Asp?Ala?Leu?Val?Glu?Ala?Val?Arg?Val?Trp?Pro?Ala?Asp?Pro?Pro?Arg

35??????????????????40??????????????????45

Asp?Pro?Lys?Gly?Trp?Leu?Val?Ala?Val?Ala?Trp?Arg?Arg?Phe?Leu?Asp

50??????????????????55??????????????????60

Ala?Ala?Arg?Ser?Asp?Ser?Ala?Arg?Arg?Arg?Arg?Glu?Asp?Ser?Val?Asp

65??????????????????70??????????????????75??????????????????80

Gly?Glu?Pro?Val?Pro?Gly?Glu?Ala?Pro?Ala?Val?Asp?Asp?Thr?Leu?Gln

85??????????????????90??????????????????95

Leu?Tyr?Phe?Leu?Cys?Ala?His?Pro?Ser?Leu?Thr?Pro?Ser?Ser?Ala?Val

100?????????????????105?????????????????110

Ala?Leu?Thr?Leu?Arg?Ala?Val?Gly?Gly?Leu?Thr?Thr?Arg?Gln?Ile?Ala

115?????????????????120?????????????????125

Gln?Ala?Tyr?Leu?Val?Pro?Glu?Ala?Thr?Met?Ala?Gln?Arg?Ile?Ser?Arg

130?????????????????135?????????????????140

Ala?Lys?Arg?Thr?Val?Ala?Gly?Val?Arg?Leu?His?Gln?Pro?Gly?Asp?Val

145?????????????????150?????????????????155?????????????????160

Ala?Thr?Val?Leu?Arg?Val?Leu?Tyr?Leu?Val?Phe?Asn?Glu?Gly?Tyr?Ser

165?????????????????170?????????????????175

Gly?Asp?Val?Asp?Leu?Ala?Ala?Glu?Ala?Ile?Arg?Leu?Thr?Arg?Gln?Leu

180?????????????????185?????????????????190

Ala?Ala?Ala?Ile?Asp?His?Pro?Glu?Val?Ala?Gly?Leu?Leu?Ala?Leu?Met

195?????????????????200?????????????????205

Leu?Leu?His?His?Ala?Arg?Arg?Thr?Ala?Arg?Thr?Ala?Pro?Asp?Gly?Ser

210?????????????????215?????????????????220

Leu?Val?Pro?Leu?Ala?Asp?Gln?Asp?Arg?Ser?Arg?Trp?Asp?Asn?Ala?Leu

225?????????????????230?????????????????235?????????????????240

Ile?Ser?Glu?Gly?Val?Ala?Val?Leu?Gln?Ala?Ala?Leu?Ser?Arg?Glu?Arg

245?????????????????250?????????????????255

Leu?Gly?Glu?Phe?Gln?Ala?Gln?Ala?Ala?Ile?Ala?Ala?Leu?His?Ala?Asp

260?????????????????265?????????????????270

Ala?Pro?Ala?Ala?Gly?Glu?Thr?Asp?Trp?Val?Gln?Ile?Val?Glu?Trp?Tyr

275?????????????????280?????????????????285

Asp?Glu?Leu?Ala?Arg?Leu?Thr?Asp?Asn?Pro?Ile?Val?Leu?Leu?Asn?Arg

290?????????????????295?????????????????300

Ala?Val?Ala?Val?Gly?Glu?Ala?Asp?Gly?Pro?Arg?Ala?Gly?Leu?Ala?Ala

305?????????????????310?????????????????315?????????????????320

Leu?Ala?Ala?Leu?Asp?Asp?Ala?Leu?Pro?Arg?His?Thr?Ala?Val?Ala?Ala

325?????????????????330?????????????????335

His?Leu?His?Glu?Arg?Asp?Gly?Asp?Arg?Ala?Arg?Ala?Ala?Arg?Leu?Tyr

340?????????????????345?????????????????350

Ala?Glu?Ala?Ala?Arg?Lys?Ala?Pro?Asn?Leu?Ala?Glu?Arg?Asp?His?Leu

355?????????????????360?????????????????365

Thr?Arg?Gln?Ala?Ala?Arg?Leu?Asn?Thr?Arg

370?????????????????375

<210>30

<211>139

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Leu?Asp?Val?Leu?Thr?Gly?Ser?Trp?Arg?Ala?Thr?Leu?Ser?Asn?Ala?Trp

1???????????????5???????????????????10??????????????????15

Phe?Leu?Glu?Pro?Pro?Asp?Gln?Glu?Val?Glu?Gly?Thr?Ala?Thr?Ala?Glu

20??????????????????25??????????????????30

Trp?Leu?Ala?Asp?Ala?Phe?Val?Val?Phe?Arg?Trp?Thr?Ile?Ser?Gly?Glu

35??????????????????40??????????????????45

Pro?Gly?Thr?Ala?Thr?Thr?Glu?Met?Val?Leu?Val?Ile?Gly?Arg?Ser?Asp

50??????????????????55??????????????????60

Ala?Asn?Asp?Ala?Tyr?Thr?Ala?Leu?Tyr?His?Asp?Glu?Arg?Gly?Val?Asn

65??????????????????70??????????????????75??????????????????80

Arg?Val?Phe?Ala?Met?Thr?Phe?Asp?Ala?Ala?Arg?Trp?Thr?Met?Ser?Arg

85??????????????????90??????????????????95

Ala?Asp?Pro?Asp?Leu?Phe?Gln?Arg?Phe?Val?Ala?Asp?Val?Thr?Pro?Gly

100??????????????????105??????????????????110

Arg?Val?Thr?Gly?Arg?Trp?Glu?Ala?Ser?Gln?Asp?Arg?Gly?Ser?Thr?Trp

115??????????????????120??????????????????125

Arg?Lys?Asp?Phe?Asp?Leu?Val?Phe?Glu?Arg?Ala

130??????????????????135

<210>31

<211>147

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Gly?Arg?Thr?Ser?Thr?Arg?Arg?Thr?Thr?Met?Ala?Lys?Tyr?Leu?Leu

1???????????????5???????????????????10??????????????????15

Leu?Lys?His?Tyr?Arg?Gly?Ala?Pro?Ala?Ala?Ala?Asn?Asp?Val?Pro?Met

20??????????????????25??????????????????30

Asp?Gln?Trp?Thr?Pro?Glu?Glu?Ile?Thr?Ala?His?Val?Gln?Tyr?Met?Arg

35??????????????????40??????????????????45

Asp?Phe?Ala?Ala?Arg?Leu?Glu?Glu?Ser?Gly?Glu?Tyr?Val?Asp?Gly?Gln

50??????????????????55??????????????????60

Ala?Leu?Ala?Pro?Glu?Gly?Met?Phe?Val?Arg?Tyr?Asp?Gly?Glu?Gly?Arg

65??????????????????70??????????????????75??????????????????80

Pro?Pro?Val?Thr?Asp?Gly?Pro?Phe?Ala?Glu?Thr?Lys?Asp?Leu?Ile?Ala

85??????????????????90??????????????????95

Gly?Trp?Met?Val?Ile?Asp?Val?Asp?Ser?Gln?Asp?Arg?Ala?Val?Glu?Leu

100?????????????????105?????????????????110

Ala?Gly?Glu?Leu?Ser?Ala?Ala?Pro?Gly?Ala?Gly?Gly?Lys?Pro?Ile?His

115?????????????????120?????????????????125

Glu?Trp?Leu?Glu?Leu?Arg?Pro?Phe?Leu?Ala?Ala?Pro?Pro?Thr?Ile?Thr

130?????????????????135?????????????????140

Glu?Cys?His

145

<210>32

<211>117

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Thr?Ile?Thr?Trp?Ser?Pro?Ala?Ser?Cys?Ser?Ala?Trp?Met?Thr?Gln

1???????????????5???????????????????10??????????????????15

Glu?Ile?Gln?Ala?Arg?Ala?Ser?Ser?Ser?Ser?Gly?Pro?Val?Gly?Ala?Gly

20??????????????????25??????????????????30

Val?Gln?Gly?Val?Pro?Ala?Lys?Arg?Ser?Thr?Pro?Arg?Ala?Ala?Lys?Arg

35??????????????????40??????????????????45

Arg?Gln?Ile?Arg?Ser?Pro?Ala?Arg?Ser?Arg?Thr?Leu?Thr?Val?Asn?Val

50??????????????????55??????????????????60

Pro?Leu?Arg?Arg?Met?Val?Gly?Gln?Val?Asp?Asp?Asp?Leu?Ala?Ala?His

65??????????????????70??????????????????75??????????????????80

Thr?Ser?Thr?Arg?Gly?Gly?Ser?Arg?Asp?Thr?Asp?Val?Ile?Glu?Leu?Gln

85??????????????????90??????????????????95

Ala?Lys?Pro?Thr?Gly?Arg?Pro?Arg?Ala?Ser?Val?Glu?Val?Thr?Met?Val

100?????????????????105?????????????????110

Thr?Pro?Val?Gly?Arg

115

<210>33

<211>151

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?His?Leu?Thr?Ile?Ile?Leu?Trp?Asp?Leu?Ala?Glu?Ser?Asp?Gln?Thr

1???????????????5???????????????????10??????????????????15

Val?Ala?Ser?Leu?Arg?Ser?Tyr?Leu?Arg?Asp?Tyr?Ala?Val?Glu?Ala?Tyr

20??????????????????25??????????????????30

Ser?Ala?Thr?Pro?Gly?Leu?Arg?Gln?Lys?Val?Trp?Val?Ala?Asn?Thr?Gly

35??????????????????40??????????????????45

Pro?Glu?Gly?Glu?Thr?Trp?Gly?Ala?Val?Tyr?Leu?Trp?Asp?Asp?Glu?Lys

50??????????????????55??????????????????60

Ala?Ala?Tyr?Gly?Arg?Pro?Pro?Gly?Val?Ser?Arg?Val?Val?Glu?Leu?Ile

65??????????????????70??????????????????75??????????????????80

Gly?Tyr?Ala?Pro?Thr?Gln?Arg?Ser?Tyr?Phe?Ser?Val?Glu?Ala?Gly?Ala

85??????????????????90??????????????????95

Asp?Gly?Pro?Leu?Ala?Gly?Ala?Leu?Ala?Gly?Leu?Gly?Leu?Ala?Phe?Thr

100?????????????????105?????????????????110

Asp?Pro?Ala?Ala?Glu?Pro?Met?Arg?Arg?Pro?Met?Glu?Phe?Asn?Pro?Pro

115?????????????????120?????????????????125

Gly?Ala?Ser?Ala?Phe?Thr?Leu?Arg?Ala?Asp?Val?Val?Ala?Gly?Ser?Pro

130?????????????????135?????????????????140

Lys?Gln?Gly?Gly?Asp?Gly?Arg

145?????????????????150

<210>34

<211>593

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ser?Ala?Asp?Thr?Arg?Cys?Phe?Ala?Val?Lys?Ala?Asp?Ala?Phe?Phe

1???????????????5???????????????????10??????????????????15

Val?Arg?His?Asp?Asp?Gly?Val?Trp?Leu?Arg?Asn?Asp?His?Gly?Ser?Phe

20??????????????????25??????????????????30

Ser?Ile?Arg?Gly?Lys?Gly?Ala?Tyr?Glu?Leu?Val?Glu?Thr?Val?Phe?Ala

35??????????????????40??????????????????45

His?Leu?Asp?Gly?Glu?Arg?Ser?Val?Ala?Asp?Leu?Cys?Ala?Gly?Leu?Pro

50??????????????????55??????????????????60

Asp?Gly?Pro?Ser?Arg?Ser?Val?Ala?Arg?Leu?Ile?Asp?Thr?Leu?Ala?Gly

65??????????????????70??????????????????75??????????????????80

Asn?Gly?Phe?Leu?Lys?Arg?Val?Glu?His?Pro?Val?Glu?His?Ala?Pro?Asp

85??????????????????90??????????????????95

Trp?Met?Arg?Glu?Arg?Tyr?Pro?Ala?His?Leu?Ala?Phe?Leu?Asp?His?His

100?????????????????105?????????????????110

Ala?Asp?Arg?Pro?Val?Thr?Arg?Met?Thr?Arg?Val?Arg?Thr?Arg?Pro?Val

115?????????????????120?????????????????125

Leu?Val?Gly?Gly?Ser?Gly?Val?Ala?Leu?Arg?Ala?Ala?Leu?Asp?Ala?Leu

130?????????????????135?????????????????140

Ala?Glu?Phe?Gly?Ile?Ala?Thr?Ala?Arg?Ile?Val?Ser?Thr?Asp?Pro?Glu

145?????????????????150?????????????????155?????????????????160

Ala?Ala?Val?Val?Val?Ala?Glu?Ala?Ala?Glu?Arg?Asp?Pro?His?Leu?Ala

165?????????????????170?????????????????175

Trp?Thr?Leu?Asp?His?Ala?Asp?Leu?Ala?Ala?Phe?Ala?Glu?Phe?Pro?Asp

180?????????????????185?????????????????190

Thr?Asp?Glu?Val?Val?Leu?Ala?Val?Asp?Asp?Ala?Asp?Pro?Ala?Ala?Leu

195?????????????????200?????????????????205

Ala?Asp?Leu?Gln?Trp?Arg?Leu?Arg?Ala?Thr?Gly?Ser?Pro?Val?Ala?Val

210?????????????????215?????????????????220

Leu?Ala?Thr?Val?Ser?Gly?Tyr?Leu?Val?Ala?Ala?Ala?Pro?Pro?Ser?Gly

225?????????????????230?????????????????235?????????????????240

Val?Asp?Trp?Cys?Trp?Glu?Cys?Val?His?Arg?Ser?Val?Val?Ala?Ala?Pro

245?????????????????250?????????????????255

Val?Gly?Gly?Ala?Thr?Gly?Leu?Ala?Pro?Ala?Ala?Thr?Pro?Ala?Ala?Leu

260?????????????????265?????????????????270

Ala?Ala?Leu?His?Val?Ala?Gln?His?Val?Phe?Ala?Arg?Leu?Ala?Glu?Val

275?????????????????280?????????????????285

Asp?Leu?Asp?Gly?Ala?Gly?Leu?Leu?Thr?Ser?Ala?Glu?Pro?Leu?Ala?Pro

290?????????????????295?????????????????300

Val?Val?Arg?Thr?His?Thr?Gly?Arg?Arg?His?Pro?Met?Cys?Arg?Arg?His

305?????????????????310?????????????????315?????????????????320

Gly?Ala?Ala?Thr?Ala?Ala?Val?Val?Glu?Arg?Val?Glu?Pro?Val?Arg?Pro

325?????????????????330?????????????????335

Asp?Val?Pro?Ala?Pro?Gln?Asp?Pro?Pro?Arg?Leu?Thr?Ala?Val?Ser?Asp

340?????????????????345?????????????????350

Arg?Ile?Val?Gly?Ala?Thr?Ala?Gly?Trp?Thr?Asp?Gln?Val?Val?Gly?Pro

355?????????????????360?????????????????365

Leu?Leu?Ser?Leu?Gly?Glu?Gly?Glu?Ala?Asp?Gln?Leu?Pro?Leu?Ser?Ala

370?????????????????375?????????????????380

Ser?Thr?Cys?Leu?Ile?Ala?Asp?Pro?Val?Glu?Arg?Ala?Ser?Arg?Leu?Leu

385?????????????????390?????????????????395?????????????????400

Val?Cys?Arg?Ala?Val?Ser?Pro?Arg?Glu?Ala?Arg?Asn?Gln?Val?Val?Leu

405?????????????????410?????????????????415

Ala?Ala?Leu?Glu?Trp?Thr?Ala?Gly?Arg?Leu?Ala?Asp?His?Gly?Val?Gly

420?????????????????425?????????????????430

Pro?Ala?Asp?Ala?Ala?Trp?Gly?Ala?Gly?Trp?Thr?Ser?Ala?Glu?Ala?Trp

435?????????????????440?????????????????445

Tyr?Arg?Ala?Val?Ala?Ala?Ala?Ser?Leu?Ala?Leu?Pro?Pro?Ala?Ser?Leu

450?????????????????455?????????????????460

Ser?Trp?Gln?Ser?Ala?Glu?Pro?His?Gly?Ala?Asp?Pro?Val?His?Gly?Phe

465?????????????????470?????????????????475?????????????????480

Leu?Thr?Asp?Thr?Leu?Ala?Ala?Glu?Gly?Arg?Pro?Trp?Thr?Ala?Thr?Ala

485?????????????????490?????????????????495

Leu?Glu?Ala?Leu?Pro?Thr?Gly?Leu?His?Arg?Ala?Arg?Val?Arg?Thr?Ala

500?????????????????505?????????????????510

Asp?Phe?Glu?Val?Ala?Glu?Gly?Val?Gly?Ile?Asp?Ala?Ala?His?Ala?Val

515?????????????????520?????????????????525

Gly?Asn?Ala?Leu?Leu?Arg?Ala?Val?Ala?Gly?Arg?Gly?Asp?Ala?Val?Ala

530?????????????????535?????????????????540

His?Leu?Ala?Pro?Pro?Val?Ala?Thr?Trp?Pro?Glu?Ala?Val?Ala?Ala?Val

545?????????????????550?????????????????555?????????????????560

Arg?Ala?Gln?Gly?Arg?Pro?Pro?Glu?Pro?Ala?Asp?Val?Thr?His?Leu?Leu

565?????????????????570?????????????????575

Pro?Phe?Leu?Gly?Asp?Ala?Ala?Cys?Leu?Ala?Ala?Ile?Pro?Gly?Gly?Ala

580?????????????????585?????????????????590

Arg

<210>35

<211>246

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Val?Gln?Pro?Thr?Ala?Val?Arg?Ala?Ala?Thr?Val?Ala?Pro?Leu?Gly?Gly

1???????????????5???????????????????10??????????????????15

Pro?Val?Phe?Asp?Gly?Pro?Gly?Leu?Asp?Glu?Thr?Thr?Arg?Gly?Phe?Leu

20??????????????????25??????????????????30

Ala?Asp?Thr?Ala?Pro?Val?Ala?Val?Asp?Leu?Ser?Thr?Arg?Pro?Asp?Arg

35??????????????????40??????????????????45

Thr?Gly?Ala?Ala?Leu?Thr?Leu?Met?Thr?Ala?His?Leu?Ala?Ala?Val?Ala

50??????????????????55??????????????????60

Asp?Pro?Ala?Arg?Ser?Gly?Asp?Gly?Pro?Pro?Leu?Ser?Phe?Leu?Ser?Phe

65??????????????????70??????????????????75??????????????????80

Arg?Ser?His?Ala?Glu?Ala?Phe?Leu?Ala?Thr?Thr?Arg?Asp?Pro?Asn?Ala

85??????????????????90??????????????????95

Ala?Arg?His?Ala?Phe?Asp?Thr?Arg?Tyr?Thr?Asp?His?Arg?Thr?Thr?Val

100?????????????????105?????????????????110

Glu?Ala?Ala?Val?Arg?Ala?Ile?Leu?Leu?Asp?Gly?Asp?Pro?Gly?Asp?Ala

115?????????????????120?????????????????125

Ala?Pro?Trp?Ser?Ala?Ala?Ala?Arg?Ala?Ala?Lys?Pro?Arg?Phe?Thr?Ala

130?????????????????135?????????????????140

Gly?Phe?Ala?Ser?Ala?Asp?Leu?Val?Ala?His?Thr?Gly?Tyr?Thr?Arg?Asp

145?????????????????150?????????????????155?????????????????160

His?Leu?Arg?Glu?Arg?Thr?Asp?Phe?Ala?Asp?Asn?Pro?Phe?His?Ser?Arg

165?????????????????170?????????????????175

Ala?Gly?Ala?Ser?Glu?Gln?Leu?Gln?Ala?Tyr?Leu?Gly?Gly?Asp?Pro?Ser

180?????????????????185?????????????????190

Phe?Leu?Ala?Thr?Arg?Leu?Leu?Thr?Ser?Leu?Leu?Tyr?Val?Thr?Leu?His

195?????????????????200?????????????????205

Ser?Ser?Gly?Val?Ser?Leu?Met?Gln?Arg?Tyr?Phe?Leu?Cys?His?Ala?Ile

210?????????????????215?????????????????220

Ala?Lys?Ala?Cys?Glu?Ser?Ile?Tyr?His?Val?Asp?Ser?Met?Ser?Leu?Leu

225?????????????????230?????????????????235?????????????????240

Ala?Asp?Leu?Ala?Val?Gly

245

<210>36

<211>135

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Gly?Val?Ala?Thr?Gln?Met?Leu?Glu?Ser?His?Pro?His?Ala?Ser?Asn

1???????????????5???????????????????10??????????????????15

Glu?Thr?Gly?Thr?Ala?Glu?Leu?Ala?Ala?Cys?Ile?Glu?Ala?Cys?Phe?Glu

20??????????????????25??????????????????30

Cys?Ala?Gln?Thr?Cys?Thr?Ala?Cys?Ala?Asp?Ala?Cys?Leu?Gly?Glu?Pro

35??????????????????40??????????????????45

Ser?Val?Ala?Glu?Leu?Val?Asp?Cys?Val?Arg?Ser?Asp?Leu?Asp?Cys?Ala

50??????????????????55??????????????????60

Asp?Val?Cys?Glu?Thr?Thr?Gly?Arg?Val?Leu?Ser?Arg?Arg?Thr?Ala?Pro

65??????????????????70??????????????????75??????????????????80

Asp?Gln?Asp?Val?Ile?Arg?Ala?Leu?Leu?Glu?Thr?Cys?Ala?Leu?Ala?Cys

85??????????????????90??????????????????95

Lys?Arg?Cys?Gly?Asp?Gln?Cys?Ala?Glu?His?Ala?Asp?His?His?Glu?His

100?????????????????105?????????????????110

Cys?Arg?Thr?Cys?Ala?Glu?Ala?Cys?Arg?Arg?Cys?Glu?Arg?Ala?Cys?Arg

115?????????????????120?????????????????125

Asp?Leu?Leu?Thr?Thr?Leu?Arg

130?????????????????135

<210>37

<211>153

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Ile?Thr?Ser?Thr?Leu?Asp?Val?Asn?Asp?Pro?Ala?Val?Glu?Arg?Asn

1???????????????5???????????????????10??????????????????15

Leu?Gly?Glu?Tyr?Val?Ala?Ala?Val?Gly?Asp?Ala?Val?Gly?Ala?Gly?Pro

20??????????????????25??????????????????30

Ala?Ala?Ser?Ala?Val?Asp?Leu?Gly?Pro?Pro?Val?Ser?Val?Tyr?Leu?Ala

35??????????????????40??????????????????45

Val?Asp?Gln?Arg?Ile?Ala?Gly?Arg?Asp?Ala?Ala?Leu?Leu?Trp?Ser?Glu

50??????????????????55??????????????????60

Arg?His?Gly?Trp?Ser?Val?Ala?Thr?Glu?Ser?His?Pro?Ala?Leu?Thr?Val

65??????????????????70??????????????????75??????????????????80

Leu?Gly?Tyr?Leu?Gly?Pro?Asp?Leu?Leu?Pro?Pro?Pro?Asn?Ala?Val?Ala

85??????????????????90??????????????????95

Arg?Phe?Leu?Ala?Asp?Ala?Val?Arg?Gly?Leu?Pro?Leu?Arg?Ile?Glu?Pro

100?????????????????105?????????????????110

Pro?His?Pro?Arg?Ser?Thr?Asp?Leu?Asp?Arg?Arg?Leu?Val?Ala?Tyr?Leu

115?????????????????120?????????????????125

Pro?Ala?Gly?Leu?Arg?Asp?Leu?Cys?Pro?Leu?Pro?Arg?Ser?Ala?Glu?Arg

130?????????????????135?????????????????140

Pro?Val?Ala?Ala?Thr?Gly?Gly?Gly?Arg

145?????????????????150

<210>38

<211>176

<212>PRT

<213>Nocardia?sp.WW-12651

<400>1

Met?Phe?Phe?Asp?Ser?Trp?Thr?Gly?Leu?Val?Arg?Val?Val?Leu?Val?Gly

1???????????????5???????????????????10??????????????????15

Leu?Pro?Ala?Tyr?Ala?Thr?Leu?Val?Leu?Ala?Leu?Arg?Leu?Ser?Gly?Lys

20??????????????????25??????????????????30

Arg?Thr?Leu?Ala?Lys?Met?Asn?Ala?Phe?Asp?Leu?Val?Val?Thr?Val?Ala

35??????????????????40??????????????????45

Leu?Gly?Ser?Thr?Leu?Ala?Thr?Ile?Leu?Leu?Thr?Ser?Asn?Val?Ala?Leu

50??????????????????55??????????????????60

Ala?Glu?Gly?Ile?Phe?Ala?Met?Ala?Val?Leu?Val?Ala?Ala?Gln?Phe?Ala

65??????????????????70??????????????????75??????????????????80

Val?Ala?Trp?Ala?Ala?Val?Arg?Ser?Pro?Arg?Ile?Arg?Arg?Ala?Val?Lys

85??????????????????90??????????????????95

Ser?Thr?Pro?Thr?Leu?Leu?Ala?Arg?His?Gly?Arg?Leu?Asp?Glu?Asp?Ala

100?????????????????105?????????????????110

Met?Arg?Glu?Gln?Arg?Val?Thr?Arg?Ser?Glu?Ile?Leu?Gln?Ala?Val?Arg

115?????????????????120?????????????????125

Ser?Ala?Gly?Ser?Gly?Gly?Leu?Asp?Gln?Val?Ala?Ala?Val?Val?Leu?Glu

130?????????????????135?????????????????140

Thr?Asp?Gly?Ser?Leu?Ser?Val?Ile?Thr?Thr?Gly?Lys?Ala?Gly?Asp?Ser

145?????????????????150?????????????????155?????????????????160

Thr?Ala?Leu?Ser?Asp?Val?Thr?Asp?Val?Pro?Arg?His?Asp?Thr?Arg?Gly

165?????????????????170?????????????????175

Claims (10)

1. one kind has the well biological synthesis gene cluster of antibiotic active microbiotic-Nuo Ka thiazole rhzomorph, and 37 the related genes of promise card thiazole rhzomorph biosynthesizing that it is characterized in that encoding are specially:

1) be responsible for the biosynthetic gene of the big ring skeleton of promise card thiazole rhzomorph I, i.e. noc28, noc20, noc 21, and noc 22, and noc 23, and noc9, noc24, noc30 be totally 8 genes:

Noc28 is positioned at 38434-38581 base place of gene cluster nucleotide sequence, and length is 150 base pairs, the precursor peptide of coding promise card thiazole rhzomorph, and length is 49 amino acid;

Noc23 is positioned at 30980-32875 base place of gene cluster nucleotide sequence, and length is 1896 base pairs, coding heterocyclization albumen, and length is 631 amino acid;

Noc22 is positioned at 29544-30983 base place of gene cluster nucleotide sequence, and length is 1440 base pairs, the coding nadh dehydrogenase, and length is 479 amino acid;

Noc21 is positioned at 26965-29523 base place of gene cluster nucleotide sequence, and length is 2559 base pairs, the coding dehydratase, and length is 852 amino acid;

Noc20 is positioned at 25968-26960 base place of gene cluster nucleotide sequence, and length is 993 base pairs, the coding dehydratase, and length is 330 amino acid;

Noc9 is positioned at 14529-14584 base place of gene cluster nucleotide sequence, and length is 456 base pairs, coding unknown function albumen, and length is 151 amino acid;

Noc24 is positioned at 32902-34683 base place of gene cluster nucleotide sequence, and length is 1782 base pairs, coding unknown function albumen, and length is 593 amino acid;

Noc30 is positioned at 40176-40916 base place of gene cluster nucleotide sequence, and length is 741 base pairs, coding unknown function albumen, and length is 246 amino acid;

2) be responsible for the biosynthetic gene of promise card thiazole rhzomorph I indolic acid side chain, i.e. noc25, noc26, noc27, noc29, totally 4 genes:

Noc27 is positioned at 36848-37948 base place of gene cluster nucleotide sequence, and length is 1101 base pairs, coding free radical SAM thiamines synthetic enzyme, and length is 366 amino acid;

Noc25 is positioned at 34680-35912 base place of gene cluster nucleotide sequence, and length is 1233 base pairs, coding acyl group-CoA synthetic enzyme, and length is 410 amino acid;

Noc26 is positioned at 35933-36820 base place of gene cluster nucleotide sequence, and length is 888 base pairs, the coding acyltransferase, and length is 295 amino acid;

Noc29 is positioned at 38714-39976 base place of gene cluster nucleotide sequence, and length is 1263 base pairs, the methyltransgerase that coding SAM relies on, and length is 420 amino acid;

3) be responsible for the biosynthetic gene of promise card thiazole rhzomorph I deoxidation glycosyl, i.e. noc6, noc10, noc11, noc12, noc13, noc14, totally 6 genes:

Noc10 is positioned at 14990-15703 base place of gene cluster nucleotide sequence, and length is 714 base pairs, the two methyltransgerases of coding N-, and length is 237 amino acid;

Noc11 is positioned at 15728-16972 base place of gene cluster nucleotide sequence, and length is 1245 base pairs, the methyltransgerase on 3 C of coding NDP-hexose, and length is 414 amino acid;

Noc12 is positioned at 16984-17970 base place of gene cluster nucleotide sequence, and length is 987 base pairs, coding NDP-hexose-3-ketoreductase, and length is 328 amino acid;

Noc13 is positioned at 17988-19418 base place of gene cluster nucleotide sequence, and length is 1431 base pairs, coding dTDP-4-ketone-6-deoxyglucose 2, and the 3-dehydratase, length is 476 amino acid;

Noc14 is positioned at 19424-20560 base place of gene cluster nucleotide sequence, and length is 1137 base pairs, the transaminase on 4 C of coding NDP-6-DDG, and length is 378 amino acid;

Noc6 is positioned at 11505-12683 base place of gene cluster nucleotide sequence, and length is 1179 base pairs, the encoding glycosyl transferring enzyme, and length is 392 amino acid;

4) Cytochrome P450 oxidoreductase gene, i.e. noc7, noc15, noc16, noc18, noc19, totally 5 genes:

Noc7 is positioned at 12704-13912 base place of gene cluster nucleotide sequence, and length is 1209 base pairs, Codocyte cytochrome p 450 oxydo-reductase, and length is 402 amino acid;

Noc15 is positioned at 20591-21703 base place of gene cluster nucleotide sequence, and length is 1113 base pairs, Codocyte cytochrome p 450 oxydo-reductase, and length is 370 amino acid;

Noc16 is positioned at 21696-22934 base place of gene cluster nucleotide sequence, and length is 1239 base pairs, Codocyte cytochrome p 450 oxydo-reductase, and length is 412 amino acid;

Noc18 is positioned at 23507-24649 base place of gene cluster nucleotide sequence, and length is 1143 base pairs, Codocyte cytochrome p 450 oxydo-reductase, and length is 380 amino acid;

Noc19 is positioned at 24646-25926 base place of gene cluster nucleotide sequence, and length is 1281 base pairs, Codocyte cytochrome p 450 oxydo-reductase, and length is 426 amino acid;

5) methyl transferase gene, i.e. noc8, noc36, totally 2 genes:

Noc8 is positioned at 13909-14532 base place of gene cluster nucleotide sequence, and length is 624 base pairs, the coding methyltransgerase, and length is 207 amino acid;

Noc36 is positioned at 43983-44768 base place of gene cluster nucleotide sequence, and length is 786 base pairs, the coding methyltransgerase, and length is 261 amino acid;

6) resistant gene, i.e. noc17, noc37, totally 2 genes:

Noc17 is positioned at 22956-23480 base place of gene cluster nucleotide sequence, and length is 525 base pairs, coding bleomycin resistance protein, and length is 174 amino acid;

Noc37 is positioned at 44914-45423 base place of gene cluster nucleotide sequence, and length is 510 base pairs, coding phosphor hydrochlorate ABC transporter, and length is 169 amino acid;

7) regulatory gene, i.e. noc5, noc33, noc34, totally 3 genes:

Noc5 is positioned at 10404-11387 base place of gene cluster nucleotide sequence, and length is 984 base pairs, the transcription regulatory protein of coding SARP family, and length is 327 amino acid;

Noc33 is positioned at 42031-42456 base place of gene cluster nucleotide sequence, and length is 426 base pairs, the coding heat shock protein(HSP), and length is 141 amino acid;

Noc34 is positioned at 42565-43173 base place of gene cluster nucleotide sequence, and length is 609 base pairs, coding hsp18 transcription regulaton factor, and length is 202 amino acid;

8) be responsible for the gene of transcription and translation, i.e. noc1, noc2, noc3, noc4 be totally 4 genes:

Noc1 is positioned at 7731-8084 base place of gene cluster nucleotide sequence, and length is 354 base pairs, coding 50S ribosomal protein L 18, and length is 117 amino acid;

Noc2 is positioned at 8282-8785 base place of gene cluster nucleotide sequence, and length is 444 base pairs, encoding D GPFAETKE family protein, and length is 147 amino acid;

Noc3 is positioned at 8731-9867 base place of gene cluster nucleotide sequence, and length is 1137 base pairs, the signal factor of coding RNA polysaccharase ECF-subtribe, and length is 378 amino acid;

Noc4 is positioned at 9968-10387 base place of gene cluster nucleotide sequence, and length is 420 base pairs, coding ATP enzyme, and length is 139 amino acid;

9) unknown function gene, i.e. noc31, noc32, noc35, totally 3 genes:

Noc31 is positioned at 41003-41410 base place of gene cluster nucleotide sequence, and length is 408 base pairs, coding unknown function albumen, and length is 135 amino acid;

Noc32 is positioned at 41492-41953 base place of gene cluster nucleotide sequence, and length is 462 base pairs, coding unknown function albumen, and length is 153 amino acid;

Noc35 is positioned at 43228-43758 base place of gene cluster nucleotide sequence, and length is 531 base pairs, coding unknown function albumen, and length is 176 amino acid.

2. the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 1 is characterized in that the precursor peptide of coding rrna mechanism in the biological synthesis gene cluster of described promise card thiazole rhzomorph comprises following two parts: signal peptide part and structural polypeptide part.

3. the proteins encoded of the biological synthesis gene cluster of a promise card thiazole rhzomorph according to claim 1 is used for catalysis synthetic antibiotic promise card thiazole rhzomorph and analogue.

4. the proteins encoded of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3 is used for catalysis synthetizing thiazolium ring.

5. the proteins encoded of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3 is used for the synthetic hydroxylation pyridine cyclic peptide center of catalysis.

6. the proteins encoded of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3 is used for catalysis synthesis of indole acid structural unit.

7. the proteins encoded of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3 is used for the big ring skeleton of the synthetic promise card thiazole rhzomorph of catalysis.

8. the proteins encoded of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3 is used for the synthetic 4-N of catalysis, N-dimethyl-2,4,6-deoxyhexamethylose.

9. the purposes of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3, portion gene are wherein carried out the complementary generation nosiheptide that recovers of allos in the mutant strain of S.actuosus ATCC 25421 genes involveds disappearance.

10. the purposes of the biological synthesis gene cluster of promise card thiazole rhzomorph according to claim 3, back modifying factor are wherein carried out the analog that heterogenous expression produces nosiheptide in S.actuosus ATCC 25421.

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