JPH0321158B2 - - Google Patents
Info
- Publication number
- JPH0321158B2 JPH0321158B2 JP17244282A JP17244282A JPH0321158B2 JP H0321158 B2 JPH0321158 B2 JP H0321158B2 JP 17244282 A JP17244282 A JP 17244282A JP 17244282 A JP17244282 A JP 17244282A JP H0321158 B2 JPH0321158 B2 JP H0321158B2
- Authority
- JP
- Japan
- Prior art keywords
- culture
- neoviridoglysein
- hyphae
- antibiotic
- strain
- 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 - Lifetime
Links
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 230000003115 biocidal effect Effects 0.000 claims description 14
- 241000187180 Streptomyces sp. Species 0.000 claims description 10
- 235000015097 nutrients Nutrition 0.000 claims description 4
- 239000002609 medium Substances 0.000 description 19
- 239000000049 pigment Substances 0.000 description 11
- 229920001817 Agar Polymers 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000008272 agar Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 229920002472 Starch Polymers 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 235000013312 flour Nutrition 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 244000068988 Glycine max Species 0.000 description 4
- 235000010469 Glycine max Nutrition 0.000 description 4
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910000160 potassium phosphate Inorganic materials 0.000 description 4
- 235000011009 potassium phosphates Nutrition 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 2
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 2
- 241000187747 Streptomyces Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 239000000306 component Substances 0.000 description 2
- 238000012136 culture method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 1
- 108010002156 Depsipeptides Proteins 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 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
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 229940078467 Prolyl hydroxylase inhibitor Drugs 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-BXKVDMCESA-N aldehydo-L-rhamnose Chemical compound C[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)C=O PNNNRSAQSRJVSB-BXKVDMCESA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000001058 brown pigment Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 229940099607 manganese chloride Drugs 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 239000012533 medium component Substances 0.000 description 1
- 239000013028 medium composition Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 239000006877 oatmeal agar Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000011218 seed culture Methods 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 229910021654 trace metal Inorganic materials 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
本発明は、抗生物質ネオビリドグリゼインの
新規な製造方法に関し、更に詳しくは、式
式中、Rは水素原子又は水酸基を表わす、
で示される抗生物質ネオビリドグリゼイン類中、
Rが水素原子であるネオビリドグリゼインを生
産する能力を有するストレプトマイセスsp.G−
89菌株を栄養培地中に培養し、培養物中に蓄積さ
れた該抗生物質を採取することを特徴とする抗生
物質ネオビリドグリゼインの生産の選択性を高
めた製造方法に関する。
従来、抗生物質ネオビリドグリゼイン類(以下
「ネオビリドグリゼイン類」と称す。)は、本発明
者等の一部によつストレプトマイセス
(Streptomyces)sp.P8648(FERM−3562)を栄
養培地に培養することによつて、ネオビリドグリ
ゼイン,,及びを同時に生産し、必要に
より各組成物を分離採取する方法が提供されてい
る(例えば、特公昭55−3339号公報参照)。
この公知の方法によれば、前記式()のRが
水酸基であるネオビリドグリゼインが主成分と
して得られ、より抗菌活性の高いネオビリドグリ
ゼインの蓄積量が少く、これらの組成比を変化
させるためには、プロリルハイドロキシレースの
阻害剤、例えば、亜鉛イオン(Zn〓)の存在下
に培養すること等が必要であつた。
本発明者等は、上記技術的課題の解決手段とし
て、ネオビリドグリゼイン類の生産菌自体のプロ
リルハイドロキシレース活性の欠損株を見い出す
べく研究した結果、該生産菌にそれ自体公知の変
異処理を施すことによつてプロリルハイドロキシ
レース活性は欠損するが、ネオビリドグリゼイン
の生合成系に関与する酵素系には変化をきたさ
ない変異菌株の取得に成功し、本発明を完成し
た。
しかして、本発明によれば、培地中にトランス
−4−ハイドロキシ−L−プロリンが存在しない
か又は微量の場合には、選択的にネオビリドグリ
ゼインを製造することができ、ネオビリドグリ
ゼインの生産は認められないか、又は極めて微
量に製造されるにすぎず、培地の効率的利用が果
たせる。
本発明に用いられる微生物は、ストレプトマイ
セスsp.P8648(FERM−p3562)を変異すること
により得たストレプトマイセスsp.G−89である。
このストレプトマイセスsp.G−89は下記の菌
学的特徴を示す。
この菌株は良く分枝した単純分枝の基生菌糸か
ら、短かい無色の気中菌糸を伸長し、その先端に
ゆるい螺旋状の胞子連鎖を形成する。その胞子の
表面は平滑であり。輪生体および子のう胞子の形
成は認められない。
各種培地における本菌株の培養的特徴は次の通
りである。
(1) シユクロース・硝酸塩寒天培地
生育:わずかに生育
気中菌糸:白色の気中菌糸を処々に薄く形成
基生菌糸:無色〜灰白色
可溶性色素:なし
(2) グルコース・アスパラギン寒天培地
生育:良好
気中菌糸:ほとんど形成せず、形成すれば白
色
基生菌糸:淡黄白色〜明黄色(2db〜2fb)
可溶性色素:なし
(3) グリセリン・アスパラギン寒天培地
生育:中程度
気中菌糸:殆んど形成せず、形成すれば白色
基生菌糸:淡黄色〜灰黄色(2db〜2dc〜
3ec)
可溶性色素:なし
(4) イースト麦芽寒天培地
生育:良好
気中菌糸:白色〜やゝ灰色を帯びた白色
基生菌糸:明るい黄色(2fb)であるが培
養後期には褐灰色(3li)となる。
可溶性色素:ないか、時には僅かに褐色を
呈す。
(5) スターチ寒天培地
生育:中程度
気中菌糸:殆んど形成しないや、形成すれば
白色
基生菌糸:淡黄色(2db)、コロニー中心部
は明るい灰黄褐色(3ge)を呈す
可溶性色素:なし
澱粉の分解:僅かに分解する
(6) チロシン寒天培地
生育:中程度
気中菌糸:殆んど形成しないや、稀に白色気
中菌糸の点在を認める。
基生菌糸:灰黄色(3ec)〜明灰黄褐色
(3ge)
可溶性色素:培養初期には薄紫色〜淡赤褐色
色素を生成するが、約10日培養で淡褐色となり、
その後薄くなる(メラニン色素を僅かに生成す
る)
(7) 栄養寒天培地
生育:良好
気中菌糸:薄く白色の気中菌糸を形成する
基生菌糸:淡黄色(2db)
可溶性色素:なし
(8) オートミール寒天培地
生育:良好
気中菌糸:白色〜灰白色
基生菌糸:灰黄色(3ec)〜明灰赤褐色
(4ge)
可溶性色素:なし
本菌株は25〜33℃を最適温度範囲として生育す
るが、20℃または37℃でも生育不良ながら生育出
来る。しかし、52℃以上では生育出来ない。本菌
株は、グルコース、ペプトン、ゼラチン培地上で
ゼラチンを液化し、無機塩、澱粉寒天培地上で、
弱いながら澱粉を加水分解する。本菌株は脱脂乳
をペプトン化する。但し凝固は認められない。本
菌株は、ペプトン・イースト・鉄・寒天培地およ
びトリプトン・イースト液体培地中では、メラニ
ン様色素を生成しないが、チロシン寒天培地中で
は時々生成する。本菌株はプリドハム・ゴツトリ
ーブ寒天培地上において、D−キシロ−ス、D−
グルコース、D−フラクトース、L−ラムノー
ス、D−マンニツトを利用し、L−アラビノー
ス、i−イノシトール、ラフイノースを利用せ
ず、シユクロースを僅かに利用する。
この菌株は形態的分類ではS(Spirales)セク
シヨンに属し、イースト・麦芽寒天培地において
白色〜明灰白色の気中菌糸を着生し、L−アラビ
ノースを利用しない。
本菌株は、昭和57年9目20日付で通商産業省工
業技術院微生物工業技術研究所に寄託され、微工
研条寄第184号(FERM−BP−184)により寄託
されている。
次に上記のストレプトマイセスsp.G−89菌株
を用いて本発明の抗生物質を製造する方法を述べ
る。上記の菌株を生産に適した栄養培地に接種
し、これを18℃ないし37℃で2日ないし14日間好
気的に培養生産し、その培養物中より抽出単離精
製する。
培地成分としては、通常のストレプトマイセス
培養に用いられている公知のものが使用出来る。
例えば炭素源としてグリコース、グリセリ、澱
粉、デキストリン、オートミール、糖蜜、油脂、
脂肪などが使用出来、窒素源としては、大豆粉、
綿実粉、ペプトン、乾燥酵母、コーンステイーブ
リカー、酵母エキス、カゼイン、カゼイン加水分
解物などの有機物ならびに硫酸アンモニウム、硝
酸アンモニウムなどの無機物が使用出来る。また
必要に応じて、炭酸カルシウム、食塩、塩化カリ
ウム、リん酸塩、硫酸マグネシウム、その他微量
金属塩などの無機塩類を添加するほか、本菌の生
育をたすけ、抗生物質ネオビリドグリゼインの生
産を促進するアミノ酸、ビタミンなどの有機物お
よび無機物を適宜添加することが出来る。また、
本菌株によりネオビリドグリゼインと同時にネ
オビリドグリゼインを製造するには、かかる培
地組成の他に、トランス−4−ハイドロキシ−L
−プロリン又はその含有物、例えば魚粉、肉エキ
ス等を添加するのがよい。
培養方法は、一般に抗生物質の生産に用いられ
ている振盪培養、タンク培養などによる液体培養
法が利用されるが、工業的生産にはタンク内深部
培養法が最も適している。
この培養は好気条件で行なわれることが望まし
く、培養温度は25〜33℃が望ましい。この方法で
本抗生物質類の生産は振盪培養、タンク培養とも
2ないし10日で最高濃度に達する。培地の種類に
よつて、培養中にpHが酸性またはアルカリ性に
大きく傾く場合があるが、この場合合には培養中
のpHを6乃至9に保つようにすることが望まし
い。
培養の始発時のpHは6.5乃至8.5に調節すること
が望ましい。
培養液中に主成分として蓄積したネオビリドグ
リゼインはデプシペプタイドを単離するための
公知の方法および、本物質の物性に基づく各種の
精製方法により純品として回収単離することが出
来る。また、必要に応じてネオビリドグリゼイン
類の混合物またはこれらとグリゼオビリデリンと
の混合物としても回収することが出来る。
本抗生物質を飼料添加剤または動物薬として調
製する場合には、特に単離することなく用いるこ
とが経済的に有利である。
培養液中に存在する抗生物質ネオビリドグリゼ
イン類は酢酸エチル、酢酸ブチル、ベンゼン、ト
ルエン、n−ブタノール、メチレンクロライド、
クロロホルム、メチルイソブチルケトンなどの難
水溶性有機溶媒により抽出される。
ネオビリドグリゼイン類は培養菌体中には殆ん
ど存在しないので、培養菌体を過または遠心分
離により、予め除去洗浄し、その洗液を含めた培
養液から本抗生物質を抽出するのが菌体中の脂
溶性不純分を除去出来るので望ましい。有機溶媒
による抽出法のほか、活性炭、アンバライト−
XAD(ローム・アンド・ハース社製)などによる
吸脱着、アンバライトIR−120(ローム・アン
ド・ハース社製)、ダウエツクス50W−X2(ダ
ウ・ケミカル社製)などの陽イオン交換樹脂によ
る吸着、溶出、セフアデツクスLH−20(フアル
マシア社製)などによるゲル過、アルミナ、シ
リカゲルなどによる吸着クロマトなどを、カラム
法または薄層法により適宜組合せて使用し、場合
によつては適当な溶媒を用いた向流分配法などを
併用して、本抗生物質を回収することが出来る。
以下に本発明を実施例により、更に詳細に述べ
る。
実施例 1
溶性澱粉2%、大豆粉0.5%、りん酸第二カリ
ウム0.1%、食塩0.1%、硫酸マグネシウム0.05%
(pH6.5に調整)からなる培地25mlを250ml溶三角
フラスコに入れ、殺菌後、ストレプトマイセス
sp.G−89を接種し、28℃で48時間ロータリー振
盪培養を行いこれを種母とした。
溶性澱粉2%、L−アスパラギン0.5%、りん
酸第二カリウム0.1%、硫酸マグネシウム0.001%
(pH6.5)からなる培地50mlを500ml容三角フラス
コに入れ、殺菌後種母を2mlずつ接種し、28℃で
144時間ロータリー振盪培養(200rpm×7cm)を
行つた。
培養液5mlをベンゼン1mlで抽出し、ベンゼン
層をシリカゲルプレート(メルク社製シリカゲル
プレートF254)にスポツトしクロロホルム:メタ
ノール=30:1の混合溶媒を用いて薄層クロマト
グラフイーを行い展開後島津製作所製クロマトス
キヤナーCS−910を用いて定量した。ネオビリド
グリゼイン類の生産量は下表1に示すとおりであ
つた。又、同様に培養したストレプトマイセス
sp.p8648(FERM P−3562)のネオビリドグリゼ
イン類の生産量を下表1に併記する。
The present invention relates to a novel method for producing the antibiotic neoviridoglysein, more specifically, the formula In the antibiotic neoviridoglyzeins represented by the formula, R represents a hydrogen atom or a hydroxyl group,
Streptomyces sp.G- which has the ability to produce neoviridoglysein in which R is a hydrogen atom
The present invention relates to a manufacturing method with enhanced selectivity for the production of the antibiotic neoviridoglysein, which is characterized by culturing 89 strains in a nutrient medium and collecting the antibiotic accumulated in the culture. Conventionally, the antibiotic neoviridoglyzeins (hereinafter referred to as "neoviridoglyzeins") have been developed by some of the present inventors as Streptomyces sp. P8648 (FERM-3562). A method has been provided for simultaneously producing neoviridoglysein, , and by culturing them in a nutrient medium, and separating and collecting each composition as necessary (for example, see Japanese Patent Publication No. 55-3339). ). According to this known method, neoviridoglysein in which R in the formula () is a hydroxyl group is obtained as a main component, and the amount of neoviridoglysein that has higher antibacterial activity accumulated is small, and the composition ratio of these is small. In order to change this, it was necessary to culture in the presence of a prolyl hydroxylase inhibitor, such as zinc ion (Zn). As a means of solving the above technical problem, the present inventors conducted research to find a strain deficient in prolyl hydroxylase activity of a neoviridoglysein producing bacterium. Through treatment, we succeeded in obtaining a mutant strain that lacks prolyl hydroxylase activity but does not cause changes in the enzyme system involved in the neoviridoglysein biosynthesis system, thereby completing the present invention. . Therefore, according to the present invention, neoviridoglysein can be selectively produced when trans-4-hydroxy-L-proline is absent or in trace amounts in the medium, and neoviridoglysein can be produced selectively. Glysein production is not observed or is only produced in extremely small amounts, allowing for efficient use of the medium. The microorganism used in the present invention is Streptomyces sp.G-89 obtained by mutating Streptomyces sp.P8648 (FERM-p3562). This Streptomyces sp.G-89 exhibits the following mycological characteristics. This strain extends short, colorless aerial hyphae from well-branched simple basal hyphae, and forms a loose spiral spore chain at the tip. The surface of the spore is smooth. No whorl or ascospore formation is observed. The culture characteristics of this strain in various media are as follows. (1) Sucrose/nitrate agar medium Growth: Slight growth Aerial hyphae: Thin white aerial hyphae formed here and there Base hyphae: Colorless to grayish white Soluble pigment: None (2) Glucose/asparagine agar medium Growth: Good Air Medium hyphae: Hardly formed, white if formed Baseline hyphae: Pale yellow-white to bright yellow (2db-2fb) Soluble pigment: None (3) Glycerin/asparagine agar medium Growth: Moderate Aerial hyphae: Most They do not form, but if they do, they are white. Base hyphae: pale yellow to gray yellow (2 db to 2 dc)
3ec) Soluble pigment: None (4) Yeast malt agar medium Growth: Good Aerial hyphae: White to slightly grayish white Base hyphae: Bright yellow (2fb), but turns brownish-gray (3li) in the later stages of culture becomes. Soluble pigment: absent or sometimes slightly brown. (5) Starch agar medium Growth: Moderate Aerial hyphae: Hardly formed, or white if formed Baseline hyphae: Pale yellow (2db), center of colony exhibits bright grayish-yellowish brown (3ge) Soluble pigment : None Starch decomposition: Slightly decomposed (6) Tyrosine agar medium Growth: Moderate Aerial hyphae: Hardly formed, or occasionally scattered white aerial hyphae are observed. Base hyphae: Gray-yellow (3ec) to light gray-yellowish brown (3ge) Soluble pigment: At the early stage of culture, it produces light purple to light reddish-brown pigment, but after about 10 days of culture, it becomes light brown.
It then becomes thinner (slightly produces melanin pigment) (7) Nutrient agar medium Growth: Good Aerial hyphae: Forms thin white aerial hyphae Base hyphae: Pale yellow (2db) Soluble pigment: None (8) Oatmeal agar medium Growth: Good Aerial hyphae: White to grayish-white Baseline hyphae: Gray-yellow (3ec) to light gray-reddish brown (4ge) Soluble pigment: None This strain grows with an optimum temperature range of 25 to 33℃, but It can grow at ℃ or 37℃ with poor growth. However, it cannot grow above 52℃. This strain liquefies gelatin on glucose, peptone, and gelatin media, and liquefies gelatin on inorganic salt and starch agar media.
Hydrolyzes starch, albeit weakly. This strain peptonizes skim milk. However, no coagulation was observed. This strain does not produce melanin-like pigments in peptone-yeast-iron-agar medium or tryptone-yeast liquid medium, but it sometimes produces melanin-like pigment in tyrosine agar medium. This strain was tested for D-xylose, D-
Glucose, D-fructose, L-rhamnose, and D-mannite are used, L-arabinose, i-inositol, and raffinose are not used, and only a small amount of sucrose is used. This strain belongs to the S (Spirales) section according to morphological classification, grows white to light grayish-white aerial hyphae on a yeast malt agar medium, and does not utilize L-arabinose. This bacterial strain was deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology, Ministry of International Trade and Industry on September 20, 1982, and has been deposited under FERM-BP-184. Next, a method for producing the antibiotic of the present invention using the Streptomyces sp.G-89 strain described above will be described. The above-mentioned strain is inoculated into a nutrient medium suitable for production, cultured aerobically at 18°C to 37°C for 2 to 14 days, and extracted and purified from the culture. As the medium components, known ones used for normal Streptomyces culture can be used.
For example, carbon sources include glycose, glycerin, starch, dextrin, oatmeal, molasses, fats and oils,
Fat, etc. can be used, and as a nitrogen source, soybean flour,
Organic substances such as cottonseed flour, peptone, dry yeast, corn stable liquor, yeast extract, casein, and casein hydrolyzate, and inorganic substances such as ammonium sulfate and ammonium nitrate can be used. In addition, as necessary, inorganic salts such as calcium carbonate, common salt, potassium chloride, phosphate, magnesium sulfate, and other trace metal salts are added, and the antibiotic neoviridoglysein is added to help the growth of this bacteria. Organic and inorganic substances such as amino acids and vitamins that promote production can be added as appropriate. Also,
In order to simultaneously produce neoviridoglysein using this strain, in addition to the above medium composition, trans-4-hydroxy-L
- It is preferable to add proline or a substance containing it, such as fish meal, meat extract, etc. As a culture method, a liquid culture method such as shaking culture or tank culture, which is generally used for the production of antibiotics, is used, but a deep culture method in a tank is most suitable for industrial production. This culture is preferably carried out under aerobic conditions, and the culture temperature is preferably 25 to 33°C. With this method, the production of the antibiotics reaches its maximum concentration in 2 to 10 days in both shaking culture and tank culture. Depending on the type of culture medium, the pH may become highly acidic or alkaline during culturing, but in this case it is desirable to maintain the pH during culturing between 6 and 9. It is desirable to adjust the pH at the beginning of culture to 6.5 to 8.5. Neoviridoglysein accumulated as a main component in the culture solution can be recovered and isolated as a pure product using known methods for isolating depsipeptides and various purification methods based on the physical properties of this substance. . Furthermore, if necessary, it can be recovered as a mixture of neoviridoglyzeins or a mixture of these and griseoviriderin. When preparing the present antibiotic as a feed additive or veterinary drug, it is economically advantageous to use it without isolation. The antibiotic neoviridoglyzeins present in the culture solution include ethyl acetate, butyl acetate, benzene, toluene, n-butanol, methylene chloride,
Extracted with poorly water-soluble organic solvents such as chloroform and methyl isobutyl ketone. Since almost no neoviridoglyseins exist in cultured bacteria, the cultured bacteria should be removed and washed in advance by filtration or centrifugation, and the antibiotic should be extracted from the culture solution including the washing liquid. It is desirable to remove fat-soluble impurities in the bacterial cells. In addition to extraction methods using organic solvents, activated carbon and amberite
Adsorption/desorption using XAD (manufactured by Rohm and Haas), adsorption by cation exchange resins such as Amberlite IR-120 (manufactured by Rohm and Haas), Dowex 50W-X 2 (manufactured by Dow Chemical), etc. , elution, gel filtration using Cephadex LH-20 (manufactured by Pharmacia), adsorption chromatography using alumina, silica gel, etc., are used in appropriate combinations using column methods or thin layer methods, and in some cases, appropriate solvents are used. This antibiotic can be recovered using a countercurrent distribution method. The present invention will be described in more detail below with reference to Examples. Example 1 Soluble starch 2%, soybean flour 0.5%, potassium phosphate 0.1%, salt 0.1%, magnesium sulfate 0.05%
(adjusted to pH 6.5) was placed in a 250 ml Erlenmeyer flask, and after sterilization, Streptomyces
sp.G-89 was inoculated and cultured with rotary shaking at 28°C for 48 hours, which was used as a seed mother. Soluble starch 2%, L-asparagine 0.5%, dibasic potassium phosphate 0.1%, magnesium sulfate 0.001%
(pH 6.5) was placed in a 500 ml Erlenmeyer flask, sterilized and inoculated with 2 ml of seedlings, and heated at 28°C.
Rotary shaking culture (200 rpm x 7 cm) was performed for 144 hours. Extract 5 ml of the culture solution with 1 ml of benzene, spot the benzene layer on a silica gel plate (Silica gel plate F 254 manufactured by Merck & Co.), perform thin layer chromatography using a mixed solvent of chloroform:methanol = 30:1, and after development use Shimadzu. Quantification was performed using Chromato Scanner CS-910 manufactured by Seisakusho. The production amount of neoviridoglyseins was as shown in Table 1 below. In addition, Streptomyces cultured in the same way
The production amount of neoviridoglyseins of sp.p8648 (FERM P-3562) is also listed in Table 1 below.
【表】
実施例 2
溶性澱粉2%、ぶどう糖0.2%、大豆粉0.5%、
トリプトン(デイフコ社製)0.4%、酵母エキス
0.2%、りん酸第二カリウム0.1%、食塩0.1%、硫
酸マグネシウム0.05%(pH6.5)の培地50mlを500
ml容三角フラスコに入れ120℃15分間殺菌後スト
レプトマイセスsp.G−89の胞子を斜面培養より
接種し、25℃にて3日間振盪培養し、これを種母
培養とした。
とうもろこし澱粉10%、大豆粉5%、りん酸第
一カリウム0.1%、食塩0.1%、硫酸マグネシウム
0.05%、塩化マンガン0.1%、硫酸亜鉛0.01%
(pH6.5)から成る培地50mlを500ml容三角フラス
コに入れ、殺菌後、上記種母培養を2%宛、接種
し、28℃に振盪培養した。
接種から5日間培養し経時的に培養液中のネオ
ビリドグリゼイン類を薄層クロマトグラフイーで
分離定量した。ストレプトマイセスsp.p8648
((FERM P−3562)を同様に培養し、両者のネ
オビリドグリゼイン類生産量を下表2に併記す
る。[Table] Example 2 Soluble starch 2%, glucose 0.2%, soybean flour 0.5%,
Tryptone (manufactured by Difco) 0.4%, yeast extract
500ml of medium containing 0.2% potassium phosphate, 0.1% potassium phosphate, 0.1% sodium chloride, 0.05% magnesium sulfate (pH 6.5)
After sterilizing the flask at 120°C for 15 minutes, Streptomyces sp. Corn starch 10%, soybean flour 5%, potassium phosphate 0.1%, salt 0.1%, magnesium sulfate
0.05%, manganese chloride 0.1%, zinc sulfate 0.01%
(pH 6.5) was placed in a 500 ml Erlenmeyer flask, and after sterilization, 2% of the above seed culture was inoculated and cultured with shaking at 28°C. After inoculation, the cells were cultured for 5 days, and neoviridoglyseins in the culture solution were separated and quantified over time using thin layer chromatography. Streptomyces sp.p8648
(FERM P-3562) was cultured in the same manner, and the production amounts of neoviridoglyseins of both are listed in Table 2 below.
【表】
以上の如く、本発明は抗生物質ネオビリドグリ
ゼイン&の生産の選択性を高めた製造法であ
る。[Table] As described above, the present invention is a manufacturing method that improves the selectivity of the production of the antibiotic neoviridoglysein &.
Claims (1)
184号)を栄養培地中に培養し、培養物中に蓄積
された式 で示される抗生物質ネオビリドグリゼインを採
取することを特徴とする抗生物質ネオビリドグリ
ゼインの製造方法。[Claims] 1. Streptomyces sp.
No. 184) was cultured in a nutrient medium, and the formula accumulated in the culture A method for producing the antibiotic neoviridoglysein, which comprises collecting the antibiotic neoviridoglysein shown in
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57172442A JPS5959198A (en) | 1982-09-29 | 1982-09-29 | Novel preparation of antibiotic neoviridogriseins |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP57172442A JPS5959198A (en) | 1982-09-29 | 1982-09-29 | Novel preparation of antibiotic neoviridogriseins |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5959198A JPS5959198A (en) | 1984-04-04 |
JPH0321158B2 true JPH0321158B2 (en) | 1991-03-22 |
Family
ID=15942056
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP57172442A Granted JPS5959198A (en) | 1982-09-29 | 1982-09-29 | Novel preparation of antibiotic neoviridogriseins |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS5959198A (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2689518B1 (en) * | 1992-04-01 | 1995-04-07 | Rhone Poulenc Rorer Sa | Microorganisms, preparation process and use. |
FR2696189B1 (en) * | 1992-09-25 | 1994-11-10 | Rhone Poulenc Rorer Sa | Polypeptides involved in the biosynthesis of streptogramins, nucleotide sequences coding for these polypeptides and their use. |
US6077699A (en) * | 1992-09-25 | 2000-06-20 | Blanc; Veronique | Polypeptides involved in the biosynthesis of streptogramins, nucleotide sequences coding for these polypeptides and their use |
-
1982
- 1982-09-29 JP JP57172442A patent/JPS5959198A/en active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS5959198A (en) | 1984-04-04 |
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