DE2151325C3 - Process for the preparation of nicotinic acid amide adenine dinucleotide phosphate - Google Patents
Process for the preparation of nicotinic acid amide adenine dinucleotide phosphateInfo
- Publication number
- DE2151325C3 DE2151325C3 DE19712151325 DE2151325A DE2151325C3 DE 2151325 C3 DE2151325 C3 DE 2151325C3 DE 19712151325 DE19712151325 DE 19712151325 DE 2151325 A DE2151325 A DE 2151325A DE 2151325 C3 DE2151325 C3 DE 2151325C3
- Authority
- DE
- Germany
- Prior art keywords
- atcc
- nicotinic acid
- acid amide
- adenine
- riboside
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- MBAJNQDWJUHYOF-UHFFFAOYSA-N 7H-purin-6-amine;pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1.NC1=NC=NC2=C1NC=N2 MBAJNQDWJUHYOF-UHFFFAOYSA-N 0.000 title claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K [O-]P([O-])([O-])=O Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- 239000010452 phosphate Substances 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims 2
- 239000001963 growth media Substances 0.000 claims description 13
- 235000005152 nicotinamide Nutrition 0.000 claims description 12
- 239000011570 nicotinamide Substances 0.000 claims description 12
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 9
- 244000005700 microbiome Species 0.000 claims description 9
- DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 8
- 229960000643 Adenine Drugs 0.000 claims description 6
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Natural products NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims description 6
- 241000186145 Corynebacterium ammoniagenes Species 0.000 claims description 6
- -1 nicotinic acid amide riboside Chemical class 0.000 claims description 6
- 241000235646 Cyberlindnera jadinii Species 0.000 claims description 5
- 230000001488 breeding Effects 0.000 claims description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
- 229960003512 nicotinic acid Drugs 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 241000191953 Kocuria varians Species 0.000 claims description 3
- 241001524178 Paenarthrobacter ureafaciens Species 0.000 claims description 3
- 241001467568 Rathayibacter rathayi Species 0.000 claims description 3
- 235000003534 Saccharomyces carlsbergensis Nutrition 0.000 claims description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 3
- 229940081969 Saccharomyces cerevisiae Drugs 0.000 claims description 3
- 241000607715 Serratia marcescens Species 0.000 claims description 3
- 229940098362 Serratia marcescens Drugs 0.000 claims description 3
- 241001454747 Streptomyces aureus Species 0.000 claims description 3
- 229960005305 adenosine Drugs 0.000 claims description 3
- SENPVEZBRZQVST-HISDBWNOSA-N deamido-NAD zwitterion Chemical compound [N+]1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP([O-])(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N2C=3N=CN=C(C=3N=C2)N)=CC=CC(C(O)=O)=C1 SENPVEZBRZQVST-HISDBWNOSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- JOUIQRNQJGXQDC-ZYUZMQFOSA-O nicotinic acid D-ribonucleotide Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)[C@@H](O)[C@@H]1[N+]1=CC=CC(C(O)=O)=C1 JOUIQRNQJGXQDC-ZYUZMQFOSA-O 0.000 claims description 3
- PUEDDPCUCPRQNY-ZYUZMQFOSA-N D-ribosylnicotinate Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1[N+]1=CC=CC(C([O-])=O)=C1 PUEDDPCUCPRQNY-ZYUZMQFOSA-N 0.000 claims description 2
- 229920001914 Ribonucleotide Polymers 0.000 claims description 2
- AANLCWYVVNBGEE-IDIVVRGQSA-L disodium [(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-3H-purin-9-yl)oxolan-2-yl]methyl phosphate Chemical compound [Na+].[Na+].O[C@@H]1[C@H](O)[C@@H](COP([O-])([O-])=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 AANLCWYVVNBGEE-IDIVVRGQSA-L 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims 1
- ZKJOXOJMGXFSPF-QYZPTAICSA-N [[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate;hydrate Chemical compound O.NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 ZKJOXOJMGXFSPF-QYZPTAICSA-N 0.000 description 9
- 239000002609 media Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N D-Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- XJLXINKUBYWONI-NNYOXOHSSA-N Nicotinamide adenine dinucleotide phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 4
- 235000013372 meat Nutrition 0.000 description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-N Nicotinamide adenine dinucleotide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 3
- 239000001888 Peptone Substances 0.000 description 3
- 108010080698 Peptones Proteins 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000019319 peptone Nutrition 0.000 description 3
- 229960001456 Adenosine Triphosphate Drugs 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 2
- 241000185996 Arthrobacter citreus Species 0.000 description 2
- 210000004185 Liver Anatomy 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K Tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N β-Alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- YOBWBLFILQYRFY-UHFFFAOYSA-M 2-hexadecylpyridine;chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCC1=CC=CC=N1 YOBWBLFILQYRFY-UHFFFAOYSA-M 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- DVARTQFDIMZBAA-UHFFFAOYSA-O Ammonium nitrate Chemical compound [NH4+].[O-][N+]([O-])=O DVARTQFDIMZBAA-UHFFFAOYSA-O 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine zwitterion Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- 229940101270 Nicotinamide adenine dinucleotide (NAD) Drugs 0.000 description 1
- FATBGEAMYMYZAF-KTKRTIGZSA-N Oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 1
- 241000235648 Pichia Species 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- JNYAEWCLZODPBN-CTQIIAAMSA-N Sorbitan Chemical compound OCC(O)C1OCC(O)[C@@H]1O JNYAEWCLZODPBN-CTQIIAAMSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- VBIIFPGSPJYLRR-UHFFFAOYSA-M Stearyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCCCC[N+](C)(C)C VBIIFPGSPJYLRR-UHFFFAOYSA-M 0.000 description 1
- 101700003082 TAOK3 Proteins 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 241000209149 Zea Species 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 229940000635 beta-Alanine Drugs 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L cacl2 Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005824 corn Nutrition 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N monochloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- 239000005445 natural product Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229940113162 oleylamide Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Description
Nicotinsäureamidadenindinucleotidphosphat
(NADP), welches auch als Coenzym II, Dehydrierungscoenzym II oder Triphosphopyridinnucleotid (TPN)
bezeichnet wird, ist eine auf biologischem Gebiet wichtige Verbindung, die folgende Strukturforme!
aufweist:Nicotinic acid amide adenine dinucleotide phosphate
(NADP), which is also known as coenzyme II, dehydration coenzyme II or triphosphopyridine nucleotide (TPN), is a compound that is important in the biological field and has the following structural forms! having:
NH,NH,
4545
OH OP(OH)2 OH OP (OH) 2
1
ο 1
ο
CONH,CONH,
60.60
ftsfts
Es ist bekannt, Nicotinsäureamidadenindinucleotidphosphat durch aerobes Züchten eines Mikroorganismus in einem Kulturmedium üblicher Zusammensetzung bei üblichen pH-Wert- und Temperaiurverhälini·»- sen herzustellen. Dabei können /. B. gemäß Chemical Abstracts Vol. 63 (19e5), Spalte 5946a, Mikroorganismen der Arten Candida utilis, Hansenula, Saccharomyces und Toliiropsis eingesetzt werden.It is known to produce nicotinic acid amide adenine dinucleotide phosphate by aerobically growing a microorganism in a culture medium of the usual composition at the usual pH and temperature ratios · »- to manufacture sen. You can use /. B. according to Chemical Abstracts Vol. 63 (19e5), column 5946a, microorganisms the species Candida utilis, Hansenula, Saccharomyces and Toliiropsis are used.
Auch ist ein Verfahren zur Herstellung von NADP durch Reaktion von Diphosphopyridinnucleotid (DPN) mit Adenosintriphosphat (ATP) in Gegenwart von DPN-Kinase von Hühnerleber bekannt (vgl. Chemical Abstracts, Vol. 73 [1970], Spalte 62 701 v). Nachteilig erscheint hierbei, daß das erforderliche Enzym aus Hühnerleber isoliert und gereinigt werden muß.Also is a process for the production of NADP by reaction of diphosphopyridine nucleotide (DPN) with adenosine triphosphate (ATP) in the presence of DPN kinase from chicken liver known (see Chemical Abstracts, Vol. 73 [1970], column 62 701 v). A disadvantage here appears that the required enzyme from Chicken liver needs to be isolated and cleaned.
Andererseits sind die beim erfindungsgemäßen Verfahren einzusetzenden Mikroorganismen gemäß der FR-PS 15 52 859 bereits unter aeroben Bedingungen in einem hierfür üblichen Kulturmedium bei hierfür üblichen pH-Wert- und Temperaturverhältnissen in Gegenwart vonOn the other hand, the microorganisms to be used in the method according to the invention are according to FR-PS 15 52 859 already under aerobic conditions in a culture medium customary for this purpose usual pH and temperature conditions in the presence of
a) Nicotinsäure und/oder Nicotinsäureamid und/oder Nicotinsäuremononucleotid und/oder Nicotinsäureamidmononucleotid und/oder Nicotinsäureibosid und/oder Nicotinsäureamidribosid und/oder Nicotinsäureadenindinucleotid unda) Nicotinic acid and / or nicotinic acid amide and / or nicotinic acid mononucleotide and / or nicotinic acid amide mononucleotide and / or nicotinic acid iboside and / or nicotinic acid amide riboside and / or nicotinic acid adenine dinucleotide and
b) Adenin und/oder Adeninribosidb) adenine and / or adenine riboside
gezüchtet worden, wobei jedoch Nicotinamidadenindinucleotid (NAD) aus der Zuchtbrühe isoliert worden ist.but nicotinamide adenine dinucleotide (NAD) has been isolated from the broth.
Demgegenüber bezieht sich die Erfindung auf ein auf der aeroben Züchtung von Mikroorganismen beruhendes Verfahren zur Herstellung von NADP.In contrast, the invention relates to one based on the aerobic cultivation of microorganisms Process for the production of NADP.
Die Erfindung besteht darin, daß man als Mikroorganismus The invention consists in that as a microorganism
Brevibacterium ammoniagenes ATCC 6871,
Brevibacterium ammoniagenes ATCC 6872,
Arthrobacter ureafaciens ATCC 7562,
Arthrobacter citreus ATCC 11 624,
Corynebacterium rathayi ATCC 13 659,
Micrococcus varians ATCC 399,
Serratia Marcescens ATCC 19 180,
Candida utilis ATCC 9950,
Saccharomyces cerevisiae ATCC 15 248 oder
Streptomyces Aureus ATCC 3309Brevibacterium ammoniagenes ATCC 6871,
Brevibacterium ammoniagenes ATCC 6872,
Arthrobacter ureafaciens ATCC 7562,
Arthrobacter citreus ATCC 11 624,
Corynebacterium rathayi ATCC 13 659,
Micrococcus varians ATCC 399,
Serratia Marcescens ATCC 19 180,
Candida utilis ATCC 9950,
Saccharomyces cerevisiae ATCC 15 248 or
Streptomyces Aureus ATCC 3309
einsetzt und die Züchtung im Kulturmedium in Gegenwart vonbegins and cultivation in the culture medium in the presence of
a) Nicotinsäure und/oder Nicotinsäureamid und/oder Nicotinsäuremononucleotid und/oder Nicotinsäureamidmononucleotid und/oder Nicotinsäureribosid und/oder Nicotinsäureamidribosid und/oder Nicotinsäureadenindinucleotid unda) Nicotinic acid and / or nicotinic acid amide and / or nicotinic acid mononucleotide and / or nicotinic acid amide mononucleotide and / or nicotinic acid riboside and / or nicotinic acid amide riboside and / or nicotinic acid adenine dinucleotide and
b) Adenin und/oder Adeninribosid und/oder Adeninribotid undb) adenine and / or adenine riboside and / or adenine ribotide and
c) einer oberflächenaktiven Substanzc) a surfactant
durchführt.performs.
Das Kulturmedium weist eine übliche Zusammensetzung auf und enthält Kohlenstoffquellen wie Glukose, Stärkehydrolysat, Melasse, Kohlenwasserstoffe, Stickstoffquellen wie Harnstoff, Ammoniumchlorid, Ammoniumnitrat, anorganischen Substanzen wie Kaliumphosphat, Magnesiumsulfat, Kaliumchlorid und stickstoffhaltige Naturstoffe wie Maiswasser, He.reextrakt, Fleischextrakt, Pepton, Fischmehl. Benötigt der jeweils verwendete Mikroorganismus für seine Züchtung besondere Nährstoffe, werden letztere dem Kulturmedium zugesetzt.The culture medium has a usual composition and contains carbon sources such as glucose, starch hydrolyzate, molasses, hydrocarbons, nitrogen sources such as urea, ammonium chloride, ammonium nitrate, inorganic substances such as potassium phosphate, magnesium sulfate, potassium chloride and nitrogen-containing natural substances such as corn water, He. r extract, meat extract, peptone, fish meal. If the microorganism used in each case requires special nutrients for its cultivation, the latter are added to the culture medium.
Die oben unter a) und b) genannten SubstanzenThe substances mentioned under a) and b) above
werden dom Kulturmedium zu Beginn der Züchtung oder iiuch einige Zeit später zugesetzt, und /war vorzugsweise in einer Menge von 50 mg/1 bis 10 g/l, Als oberflächenaktive Substanzen, die vorzugsweise in einer Konzentration von 0,01 bis 0,5% eingesetzt werden, können kationische wieare added to the culture medium at the beginning of cultivation or some time later, and / was preferably in an amount of 50 mg / 1 to 10 g / l, as surface-active substances, which are preferably used in a concentration of 0.01 to 0.5% can be used, cationic such as
Cetyltrimethylammoniumbromid,
Cetylpyridinchlorid,
Trimethyloctadecylammoniumchlorid,
Alkyldimethylbenzylammoniumchlorid,
Polyoxyäthylenalkylamin, Derivate von
Hydroxyäthylglyoxalizin,
Lauryltrimethylammoniumchlorid,
Polyoxyäthylenstearylamin, anionische wie
Natriumlaurylsulfat, Natriumoleylamidsulfat
und nichtionische wie
Trioxyäthylensorbitanmonostearat,
TrioxyäthylensorbitanmonopalnrtatCetyltrimethylammonium bromide,
Cetyl pyridine chloride,
Trimethyloctadecylammonium chloride,
Alkyldimethylbenzylammonium chloride,
Polyoxyethylene alkylamine, derivatives of
Hydroxyethylglyoxalizine,
Lauryltrimethylammonium chloride,
Polyoxyethylene stearylamine, anionic such as
Sodium lauryl sulfate, sodium oleyl amide sulfate
and non-ionic like
Trioxyethylene sorbitan monostearate,
Trioxyethylene sorbitan monopalinate
verwendet werden.be used.
Die aerobe Züchtung, die in einer Schüttelkultur oder Unterwasserkultur mit Belüften und Rühren vorgenommen werden kann, wird vorzugsweise bei einem pH von 5,5 bis 9,0 und bei einer Temperatur von 20 bis 40° C für 2 bis 8 Tage durchgeführt. Das im Kulturmedium angesammelte NADP kann nach bekannten Methoden isoliert werden, z. B. unter Verwendung eines Ionenaustauscherharzes oder durch Adsorption.Aerobic cultivation carried out in a shaking culture or underwater culture with aeration and stirring is preferably at a pH of 5.5 to 9.0 and at a temperature of 20 to 40 ° C for 2 carried out up to 8 days. The NADP that has accumulated in the culture medium can be removed by known methods be isolated, e.g. B. using an ion exchange resin or by adsorption.
Die durch die Erfindung erreichten Vorteile sind darin zu sehen, daß auf einfache Weise NADP in hoher Ausbeute gewonnen werden kann, was auch die nachfolgenden Ausführungsbeispiele zeigen.The advantages achieved by the invention are to be seen in the fact that in a simple manner NADP in high Yield can be obtained, which is also shown by the following exemplary embodiments.
Es wurde ein Nährmedium aus 3% Glukose, 1% Fleischextrakt, 1% Pepton und 0,25% NaCl zubereitet und mit Natronlauge auf einen pH-Wert von 7,5 eingestellt. Das Nährmedium wurde in 300-ml-Portionen unterteilt, in konische 2-Liter-Kolben eingebracht und danach durch Erhitzen sterilisiert. Getrennt sterilisierter Harnstoff wurde in einer Menge von 0,25 Gew. % dem Nährmedium zugesetzt, welches anschließend mit Brevibacterium ammoniagenes ATCC 6872 beimpft würde. Das beimpfte Nährmedium wurde dann bei 2i\°C 24 Std. lang unter Schütteln gezüchtet, so daß man eine Impfkultur erhielt.A nutrient medium was prepared from 3% glucose, 1% meat extract, 1% peptone and 0.25% NaCl and adjusted to a pH of 7.5 with sodium hydroxide solution. The nutrient medium was divided into 300 ml portions, placed in 2 liter conical flasks and then sterilized by heating. Separately sterilized urea was added in an amount of 0.25% by weight to the nutrient medium, which was then inoculated with Brevibacterium ammoniagenes ATCC 6872. The inoculated nutrient medium was then grown at 21 ° C. for 24 hours with shaking, so that an inoculum was obtained.
Alsdann wurde ein Kulturmedium aus 14% Glukose, 0,6% Fleischextrakt, 1.4% K2HPO4,1,4% KH2PO4.1,4% MgSO4, 0,01% CaCI2, 0,001% FeSO4, 0,001% ZnSO4, 20 mg/1 1-Cystin, 5 mg/1 ß-Alanin, 30 μg/l Biotin, 5 mg/1 Thiarnin und lOO^ig/l MnSO4 zubereitet, auf einen pH-Wert von 7,0 eingestellt und anschließend zur Sterilisierung gekocht. Daraufhin wurde noch 0,2% steriliserter Harnstoff zugesetzt.Then a culture medium consisting of 14% glucose, 0.6% meat extract, 1.4% K 2 HPO 4 , 1.4% KH 2 PO 4, 1.4% MgSO 4 , 0.01% CaCl 2 , 0.001% FeSO 4 , 0.001% ZnSO 4 , 20 mg / 1 1-cystine, 5 mg / 1 ß- alanine, 30 μg / l biotin, 5 mg / 1 thiarnin and 100 ^ ig / l MnSO 4, prepared to a pH value of 7, 0 and then boiled for sterilization. Then 0.2% sterilized urea was added.
Das so präparierte Kulturmedium (3 Liter) wurde mit '/ίο des Volumens Impfkultur beimpft und in einen 5-üter-Glasfermenter eingefüllt. Das beimpfte Kulturmedium wurde dann bei 32°C unter Rühren (650 U.p.M.) und Belüften (3 Liter/Min.) gezüchtet, wobei der pH-Wert mit NH3 auf 7,0 gehalten wurde. Nach 30 Std. Züchten wurden je 3 g/l (Konzentration nach Zusatz) Adenin und Nikotinsäure, die beide getrennt sterilisertThe culture medium prepared in this way (3 liters) was inoculated with '/ ίο the volume of inoculum and in a Filled 5-uter glass fermenter. The inoculated culture medium was then stirred at 32 ° C (650 r.p.m.) and aeration (3 liters / min.), keeping the pH at 7.0 with NH3. After 30 hours Cultures were each 3 g / l (concentration after addition) adenine and nicotinic acid, both of which were sterilized separately
waren, zugeseizt. Außerdem wurden nach weiteren 48 Std, Züchten 2 g/l (Konzentration nach Zusatz) einer handelsüblichen von Hydroxyäthylglyoxalizin abgeleiteten oberflächenaktiven Substanz zugesetzt, welche getrennt steriliseri worden war. Danach wurde noch weitere 96 Sld. gezüchtet. In der Zuchtbrühe wurden 0,8 g/l NADP angesammelt, die durch Ionenaustauscherbehandlung isoliert wurden.were interested. In addition, after another 48 hours of cultivation, 2 g / L (concentration after addition) became one commercial surface-active substance derived from Hydroxyäthylglyoxalizin added, which had been sterilized separately. Then another 96 Sld. bred. In the broth were 0.8 g / l of NADP was accumulated, which was isolated by ion exchange treatment.
Das Züchten wurde auf die im Beispiel 1 beschriebene Weise ausgeführt, jedoch wurden die Nikotinsäure durch 3 g/l Nikotinsäureamid und das genannte oberflächenaktive Mittel durch 2,5 g/l Polyoxyäthylenalkylamin ersetzt. Es wurden 1,2 g/l NADP in der Zuchtbrühe angesammelt.Cultivation was carried out in the same manner as described in Example 1, except that the nicotinic acid became with 3 g / l nicotinic acid amide and the surface-active agent mentioned with 2.5 g / l polyoxyethylene alkylamine replaced. 1.2 g / l NADP was accumulated in the breeding broth.
Es wurde auf die im Beispiel 1 beschriebene Weise eine Impfkultur bereitet. Ein Medium, das aus 3% Glukose, 1% Fleischextrakt, 1 % Pepton, 0,1% K2HPO4, 0,1% KH2PO4, 0,1% MgSO4, 0,002% FeSO4, 0,001% ZnSO4, 5 mg/1 j3-Alanin, 5 μg/l Biotin, 0,5 mg/1 Thiamin und 100 μg/l MnSO4 bestand, wurde in einem 200-üter-Fermenter mit Natronlauge auf einen pH-Wert von 7,2 eingestellt und durch Kochen sterilisiert. 1001 des Mediums wurden mit '/% des Volumens Impfkultur beimpft, und es wurde unter Rühren (250 U.p.M.) und Belüften v60 üter/Min.) bei 32°C gezüchtet.An inoculum was prepared in the manner described in Example 1. A medium consisting of 3% glucose, 1% meat extract, 1% peptone, 0.1% K 2 HPO 4 , 0.1% KH 2 PO 4 , 0.1% MgSO 4 , 0.002% FeSO 4 , 0.001% ZnSO 4, 5 mg / 1 j3-alanine, 5 g / l biotin, 0.5 mg / 1 thiamine and 100 ug / l MnSO 4 consisted was, in a 200-Ueter fermenter with sodium hydroxide to a pH of 7 2 set and sterilized by boiling. 1001 of medium were inoculated with '/% of the volume of seed culture, and it was added under stirring (250 rpm) and aeration v 60 Ueter / min.) At 32 ° C grown.
Nach 18 Std. Züchten wurden 1001 des Zuchtmediums auf 1000 Liter eines Kulturmediums, das auf die in Beispiel 1 beschriebene Weise bereitet war, in einem 2000-Liter-Fermenter geimpft. Nach 24 Std. Züchten wurde Glukose in einer Konzentration von 7,5% (nach Zusatz) zugegeben. Die Züchtung wurde auf die im Beispiel 2 beschriebene Weise weitere 96 Std. fortgesetzt, wobei sich 1,8 g/l NADP in der Zuchtbrühe ansammelten.After 18 hours of cultivation, 1001 of the cultivation medium became to 1000 liters of a culture medium, which was prepared in the manner described in Example 1, in one 2000 liter fermenter inoculated. After 24 hours of cultivation, glucose was released at a concentration of 7.5% (according to Addition) added. Cultivation was continued in the manner described in Example 2 for a further 96 hours. continued, with 1.8 g / L NADP accumulating in the broth.
Die nachfolgend aufgeführten Mikroorganismen wurden auf die im Beispiel 1 beschriebene Weise gezüchtet — mit dem einzigen Unterschied, daß der pH-Wert des Kulturmediums für Candida utilis ATCC 9950 mit NH3 auf 6,0 gehalten wurde. Nach Vollendung der Züchtung hatten sich. in der Zuchtbrühe die nachfolgend angegebenen Mengen NADP angesammelt: The microorganisms listed below were grown in the manner described in Example 1 - with the only difference that the pH of the culture medium for Candida utilis ATCC 9950 was kept at 6.0 with NH 3. After the breeding had been completed. the following amounts of NADP accumulated in the breeding broth:
Claims (1)
Brevibacterium ammoniagenes ATCC 6872,
Arthrobacter ureafaciens ATCC 7562,
Arhtrobacter citreus ATCC 11 624,
Corynebacterium rathayi ATCC 13 659,
Micrococcus Varians ATCC 399,
Serratia marcescens ATCC 19 180,
Candida utilis ATCC 9950,
Saccharomyces cerevisiae ATCC 15 248 oder
Streptomyces aureus ATCC 3309Brevibacterium ammoniagenes ATCC 6871,
Brevibacterium ammoniagenes ATCC 6872,
Arthrobacter ureafaciens ATCC 7562,
Arhtrobacter citreus ATCC 11 624,
Corynebacterium rathayi ATCC 13 659,
Micrococcus Varians ATCC 399,
Serratia marcescens ATCC 19 180,
Candida utilis ATCC 9950,
Saccharomyces cerevisiae ATCC 15 248 or
Streptomyces aureus ATCC 3309
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9391070 | 1970-10-27 | ||
| JP45093910A JPS5133191B1 (en) | 1970-10-27 | 1970-10-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2151325A1 DE2151325A1 (en) | 1972-05-04 |
| DE2151325B2 DE2151325B2 (en) | 1976-11-18 |
| DE2151325C3 true DE2151325C3 (en) | 1977-07-07 |
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