JPH0468319B2 - - Google Patents
Info
- Publication number
- JPH0468319B2 JPH0468319B2 JP60108427A JP10842785A JPH0468319B2 JP H0468319 B2 JPH0468319 B2 JP H0468319B2 JP 60108427 A JP60108427 A JP 60108427A JP 10842785 A JP10842785 A JP 10842785A JP H0468319 B2 JPH0468319 B2 JP H0468319B2
- Authority
- JP
- Japan
- Prior art keywords
- antibiotic
- spectrum
- culture
- medium
- acetonitrile
- 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 19
- 230000003115 biocidal effect Effects 0.000 claims description 17
- 238000000862 absorption spectrum Methods 0.000 claims description 8
- 238000010521 absorption reaction Methods 0.000 claims description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 241000187747 Streptomyces Species 0.000 claims description 2
- 244000005700 microbiome Species 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000002609 medium Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 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 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 239000001888 Peptone Substances 0.000 description 5
- 108010080698 Peptones Proteins 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 235000019319 peptone Nutrition 0.000 description 5
- 241000186361 Actinobacteria <class> Species 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 238000005273 aeration Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 238000012258 culturing Methods 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
- 239000001963 growth medium Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000013372 meat Nutrition 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000020183 skimmed milk Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- GMKMEZVLHJARHF-UHFFFAOYSA-N (2R,6R)-form-2.6-Diaminoheptanedioic acid Natural products OC(=O)C(N)CCCC(N)C(O)=O GMKMEZVLHJARHF-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000193468 Clostridium perfringens Species 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-SOOFDHNKSA-N D-ribopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@@H]1O SRBFZHDQGSBBOR-SOOFDHNKSA-N 0.000 description 2
- 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 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 244000068988 Glycine max Species 0.000 description 2
- 235000010469 Glycine max Nutrition 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- GMKMEZVLHJARHF-SYDPRGILSA-N meso-2,6-diaminopimelic acid Chemical group [O-]C(=O)[C@@H]([NH3+])CCC[C@@H]([NH3+])C([O-])=O GMKMEZVLHJARHF-SYDPRGILSA-N 0.000 description 2
- -1 methanol and ethanol Chemical compound 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011218 seed culture Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 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
- 239000004254 Ammonium phosphate Substances 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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-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
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 241000233866 Fungi Species 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
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 241000699670 Mus sp. Species 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
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 241000382353 Pupa Species 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
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 241000576755 Sclerotia Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 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
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- 150000001298 alcohols Chemical class 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
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 150000003863 ammonium salts 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
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- DLRVVLDZNNYCBX-ZZFZYMBESA-N beta-melibiose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)O1 DLRVVLDZNNYCBX-ZZFZYMBESA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 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 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- ARPLKSKOWFTTTQ-UHFFFAOYSA-L cobalt(2+);dichloride;dihydrate Chemical compound O.O.Cl[Co]Cl ARPLKSKOWFTTTQ-UHFFFAOYSA-L 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N deuterated acetone Substances [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral 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
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SURQXAFEQWPFPV-UHFFFAOYSA-L iron(2+) sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Fe+2].[O-]S([O-])(=O)=O SURQXAFEQWPFPV-UHFFFAOYSA-L 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000013587 production medium Substances 0.000 description 1
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 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
- 150000003839 salts Chemical class 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
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 230000019086 sulfide ion homeostasis Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001446247 uncultured actinomycete Species 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- RZLVQBNCHSJZPX-UHFFFAOYSA-L zinc sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Zn+2].[O-]S([O-])(=O)=O RZLVQBNCHSJZPX-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
Description
(産業上の利用分野)
本発明は、新規な抗生物質SK−1071およびそ
の製造法に関するものである。
(発明の構成)
本発明者らは、放線菌の生産する抗生物質の探
索の過程において、新たに土壌より分離した一放
線菌SK−1071が嫌気性細菌などに有効な新規抗
生物質を生産することを見い出した。本生産菌株
の同定および本物質を単離した後、理化学的およ
び生物学的性質を調べることにより本発明を完成
した。
本発明に係る構成物質SK−1071の理化学的性
状は、次のとおりである。
(1) 元素分析:C60.50% H6.07%
(2) 分子量:630、高分解能マススペクトルでの
分子イオンピーク、m/z630、2315、元素分析
およびC−13核磁気共嗚スペクトル(第4図)
から分子式C32H33O13が求められる。
(3) 融点:130−233℃
(4) 比旋光度:〔α〕18 D−0.1゜(C=1、アセトニ
ト
リル)
(5) 紫外線吸収スペクトル:50%アセトニトリル
水溶液中で277nmおよび350nmに吸収極大を示
し、分子吸光係数はそれぞれ6170、4660(第1
図)。
(6) 赤外線吸収スペクトル:第2図のとおりであ
る。(KBr法)
(7) プロトン核磁気共嗚スペクトル:第3図のと
おりである。
(8) C−13核磁気共嗚スペクトル:第4図のとお
りである。
(9) 溶剤に対する溶解性は、アセトニトリル、ア
セトン、酢酸エチルに可溶であり、水、n−ヘ
キサンに不溶である。
(10) 呈色反応は、過マンガン酸カリ、H2SO4に
陽性、ドラーゲンドルフ、ニンヒドリンに陰性
である。
(11) 酸性物質である。
上記の理化学的性質および後述する生物活性を
有する点で、既知の抗生物質は存在しないので、
本発明による新規抗生物質をSK−1071と命名し
た。
本物質の生物学的性質は、次のとおりである。
(1) 抗菌性
寒天希釈法による最小阻止濃度(MIC)は、
第1表に示すとおりである。
(Industrial Application Field) The present invention relates to a novel antibiotic SK-1071 and a method for producing the same. (Structure of the Invention) In the process of searching for antibiotics produced by actinomycetes, the present inventors discovered that actinomycetes SK-1071, which was newly isolated from soil, produced a new antibiotic effective against anaerobic bacteria. I discovered that. After identifying the production strain and isolating the substance, the present invention was completed by investigating its physicochemical and biological properties. The physical and chemical properties of the constituent material SK-1071 according to the present invention are as follows. (1) Elemental analysis: C60.50% H6.07% (2) Molecular weight: 630, molecular ion peak in high-resolution mass spectrum, m/z 630, 2315, elemental analysis and C-13 nuclear magnetic resonance spectrum (second Figure 4)
The molecular formula C 32 H 33 O 13 can be found from (3) Melting point: 130-233℃ (4) Specific rotation: [α] 18 D -0.1゜ (C=1, acetonitrile) (5) Ultraviolet absorption spectrum: Maximum absorption at 277nm and 350nm in 50% acetonitrile aqueous solution The molecular extinction coefficients are 6170 and 4660 (first
figure). (6) Infrared absorption spectrum: As shown in Figure 2. (KBr method) (7) Proton nuclear magnetic resonance spectrum: As shown in Figure 3. (8) C-13 nuclear magnetic resonance spectrum: As shown in Figure 4. (9) Solubility in solvents: soluble in acetonitrile, acetone, and ethyl acetate, and insoluble in water and n-hexane. (10) Color reaction is positive for potassium permanganate and H 2 SO 4 and negative for Dragendorff and ninhydrin. (11) It is an acidic substance. Since there are no known antibiotics that have the above-mentioned physicochemical properties and the biological activities described below,
The novel antibiotic according to the present invention was named SK-1071. The biological properties of this substance are as follows. (1) Antibacterial properties The minimum inhibitory concentration (MIC) determined by the agar dilution method is
As shown in Table 1.
【表】
(2) 毒性
本抗生物質をマウス腹腔内投与した場合の
LD59は100mg/Kg以上である。
本発明の抗生物質SK−1071を生産するために
使用される微生物の実用的な例は、本発明者によ
つて土壌から分離された放線菌SK−1071株があ
げられる。この菌は、工業技術院微生物工業技術
研究所に受託番号「微工研菌寄第8107号」として
寄託されている。その菌学的性状は、次のとおり
である。
() 形態的性状
SK−1071株の栄養菌糸は、各種寒天培地でよ
く発達し、通常は隔壁を有しない。気菌糸は各種
寒天培地で豊富に着先し、ビロード状あるいは粉
状を呈する。顕微鏡下の観察では、気菌糸は螺旋
状を呈し、20ケ以上の胞子による長い連鎖を形成
する。胞子は円筒形で、表面は毛状である。胞子
の大きさは1.2×0.7μmである。菌核、胞子のうお
よび遊走子は観察されない。
() 各種培地上での培養性状
イ−・ビー・シヤーリング(E.B.Shirling)お
よびデイー・ゴツトリーブ(D.Gottlieb)の方法
〔インターナシヨナル・ジヤーナル・オブ・シス
テイマテツク・バクテリオロジ−(Int.J.Syst,
Bacteriol.)16,313(1966)〕によつて調べた本
生産菌の培養性状を次表に示す。色調は標準色と
して、カラー・ハーモニー・マニユアル(Color
Harmony Manual)第4版〔コンテナー・コー
ポレーシヨン・オブ・アメリカ(Container
Corporation of America)1958年〕を用いて決
定し、色票名とともに括弧内にそのコードを併せ
て記した。以下は特記しない限り、27℃、2週間
目の各培地における観察の結果である。[Table] (2) Toxicity When this antibiotic was administered intraperitoneally to mice,
LD 59 is 100 mg/Kg or more. A practical example of the microorganism used to produce the antibiotic SK-1071 of the present invention is the actinomycete strain SK-1071, which was isolated from soil by the present inventor. This bacterium has been deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology under the accession number ``Feikoken Bacteria No. 8107''. Its mycological properties are as follows. () Morphological characteristics The vegetative hyphae of strain SK-1071 develop well on various agar media and usually do not have septa. Aerial mycelium is abundant on various agar media and appears velvety or powdery. When observed under a microscope, aerial hyphae appear spiral-shaped and form long chains of 20 or more spores. The spores are cylindrical and have a hair-like surface. The size of the spores is 1.2 x 0.7 μm. No sclerotia, sporangia and zoospores are observed. () Culture properties on various media Methods of EBShirling and D. Gottlieb [International Journal of Systematic Bacteriology (Int.J.Syst,
Bacteriol.) 16 , 313 (1966)], the culture properties of this producing bacterium are shown in the following table. The color tone is the standard color, and the Color Harmony Manual (Color
Harmony Manual) 4th Edition [Container Corporation of America
Corporation of America) in 1958], and the code is written in parentheses along with the color chart name. The following are the results of observations on each culture medium at 27°C for 2 weeks unless otherwise specified.
【表】【table】
【表】【table】
【表】
選定の培地
() 生理学的諸性質
(1) メラニン色素の生成
(イ) チロシンン寒天 陰性
(ロ) ペプトン・イースト鉄寒天 陰性
(ハ) グルコース・ベプトン・ゼラチン培地
(穿刺(21〜23℃) 陰性
(ニ) トリプトン・イースト液 陰性
(2) チロシナーゼ反応 陰性
(3) 硫化水素の生産 陰性
(4) 硝酸塩の還元 陽性
(5) ゼラチンの液化(21〜23℃)
(グルコース・ペプトン・ゼラチン培地)陰性
(6) スターチの加水分解 陽性
(7) 脱脂乳の凝固(37℃) 陰性
(8) 脱脂乳のペプトン化(37℃) 陽性
(9) 生育温度範囲 15〜45℃
(10) 炭素源の利用性
(プリーダム・コドリーブ寒天培地)
利用する:D−グリコース、L−アラビノー
ス、D−キシロース、ラフイノース、メ
リビオース、D−マンニトール、D−フ
ルクトース、L−ラムノース、i−イノ
シトール、シユークロース
(11) セルロースの分解 陰性
() 細胞の化学成分
ジアミノピメリン酸はLL型であり、全菌体の
糖の分析ではアラビノースとガラクトースが認ら
れた。
以上、本菌の菌学的性状を要約すると、次のと
おりになる。
細胞壁組成としてLL−ジアミノピメリン酸を
有する。また、形態的には、螺旋状の胞子鎖を形
成し、胞子の表面は毛状である。培養上の諸性質
としては、栄養菌糸はバンプーあるいはライトア
イボリーの色調を呈し、気菌糸はプラウニツシユ
グレイの色調を呈する。可溶性色素は生産しな
い。
これらの結果から、本菌はStreptomyces属に
属し、テイー・ジー・プリドハム(T.G.
Pridham)とエイチ・デー・トレスナー(H.D.
Tresner)の分類〔バージエーズ・マニユアル・
オブ・デタミネーテイブ・バクテリオロジイ
(Bergey′sManual of Determinative
Bacteriology)第8版,748〜829頁,1974年〕
によるグレイシリーズに属する菌種と考えられ
る。
上記菌株の変異株も本発明の方法に使用するこ
とができる。
培地としては、放線菌の培養に適する炭素源、
窒素源、無機物、必要に応じてその他の栄養物を
ほどよく含有する合成培地または天然培地を使用
することができる。
培地に使用される炭素源、窒素源は、使用菌株
の利用可能なものならばいずれの種類でもよい。
すなわち、炭素源としては、たとえば、グルコー
ス、グリセロール、フラクトース、マルトース、
マンニツト、キシロース、ガラクトース、リボー
ス、澱粉またはその加水分解物等の種々の炭水化
物が使用できる。その濃度は通常、培地に対して
0.1〜5%(グルコース換算)が好ましい。また、
グルコン酸、ピルビン酸、乳酸、酢酸等の各種有
機酸、グリシン、グルタミン酸、アラニン等の各
種アミノ酸、さらにはメタノール、エタノール等
のアルコール類や、ノルマルパラフイン等の各種
の非芳香族系炭化水素、あるいは植物性もしくは
動物性の各種油脂等も使用可能である。窒素源と
しては、アンモニア、塩化アンモニウム、燐酸ア
ンモニウム、硫酸アンモニウム、硝酸アンモニウ
ム等の各種の無機酸あるいは有機酸のアンモニウ
ム塩類、尿素、ペプトン、NZ−アミン、肉エキ
ス、酵母エキス、乾燥酵母、コーンスチープリカ
ー、カゼイン加水分解物、フイツシユミールある
いはその消化物、大豆粉あるいはその消化物、脱
脂大豆あるいはその消化物、蛹加水分解物等の含
窒素有機物質、さらにはグリシン、グルタミン
酸、アラニン等の各種アミノ酸が使用可能であ
る。
無機物としては各種燐酸塩、硫酸マグネシウ
ム、食塩等、さらに微量の重金属塩が使用され
る。
また、栄養要求性を示す変異株を用いる場合に
は、当然その栄養要求を満足させる物質を培地に
加えなければならないが、この種の栄養素は、天
然物を含む培地を使用する場合には、とくに添加
を必要としない場合がある。
発酵は振盪培養または通気撹拌深部培養等の好
気的条件下で行なう。培養温度は通常20〜40℃で
ある。培養期間は通常1〜8日で、菌体内外に抗
生物質SK−1071が生成蓄積する。
培養終了後に培養物より抗生物質SK−1071を、
たとえば、次の方法で採取する。培養物を遠心分
離により、液と沈澱物とに分離する。液から
は活性炭、多孔性合成高分子樹脂、イオン交換樹
脂等に吸着させ、溶出させることにより抽出す
る。沈澱物からは酢酸エチルまたはノルマルブタ
ノールや含水アセトン等の有機溶媒で抽出する。
抽出物を適宜濃縮乾固することにより、SK−
1071の粗物質を得る。粗物質はさらに、脂溶性物
質の精製において通常用いられる公知の方法、た
とえば、シリカゲルカラムクロマトグラフイー等
の濃縮法などを適宜組合わせることにより精製さ
れる。これらの精製方法で得られる活性画分を濃
縮乾固することにより、抗生物質SK−1071の粉
末を得ることができる。
本発明において、抗生物質SK−1071の検出お
よび定量は、シリカゲル薄層クロマトグラフイー
(メルク社製シリカゲル60F254、厚さ0.2nm、展
開溶媒ベンゼン/アセトン=3:1、抗生物質
SK−1071のRf値0.40)およびクロストリジウ
ム・パーフリンゲンス(Clostridium perfri−
ngens)ATCC3624を用いる生物学的検定法によ
つた。
(発明の効果)
上記のとおり抗生物質SK−1071は毒性が低く、
主として嫌気性細菌に活性を示す。したがつて、
本物質は、ヒトおよび動物の微生物感染症に対す
る治療薬、予防薬としての使用が期待される。
(実施例)
次に、本発明の抗生物質SK−1071の実施例を
示すが、この実施例は単なる一例を示すものであ
つて、本発明を限定するものではない。
放線菌SK−1071株(微工研寄第8107号)の斜
面培養から一白金耳を100mlの種培地(グルコー
ス0.1%、スターチ2.4%、ペプトン0.3%、肉エキ
ス0.3%、酵母エキス0.5%、炭酸カルシウム0.4
%)を入れた500ml容の坂口フラスコに接種し、
27℃で2日間振盪培養して種培養を得た。こ種培
養400mlを、40の生産培地(グルコース0.1%、
スターチ2.4%、ペプトン0.3%、肉エキス0.3%、
酵母エキス0.5%、炭酸カルシウム0.4%、硫酸第
一鉄7水塩1mg/、塩化マンガン4水塩1mg/
、硫酸亜鉛7水塩1mg/、硫酸銅5水塩1
mg/、塩化コバルト2水塩1mg/を入れた30
容ジヤーフアメンター2基に分けて接種し、27
℃で3日間通気撹拌培養(通気量10/mm、撹拌
250rpm)を行なつた。
培養液40をシヤープレス型遠心分離機を用い
て遠心分離し、菌体と培養上清に分離する。菌体
に90%アセトン溶液2.5を加え撹拌し、再抽出
を行なつた。
このアセトン溶液を減圧下で濃縮し、アセトン
を除去した後、培養上清18と合わせ、塩酸でPH
4に調整した。これを650mlのダイカイオンHp−
20を充填したカラムに通した後、70%アセトン水
で溶出し、1ずつ分画した。活性画分(No.1〜
3)を集めて減圧下濃縮し、アセトンを除去した
後、塩酸でPH3に調整し、1の酢酸エチルで回
抽出した。抽出液を減圧下で濃縮乾固することに
より、タール状物質840mgを得た。
タール状物質840mgをメタノールに溶解しセラ
イトと混合した後、濃縮乾固した。この粉末を3
mlベンゼンに懸濁し、あらかじめベンゼンに懸濁
させたシリカゲル(40g、メルク社製,
Art.9385)を充填したカラム上端に添加した。カ
ラムをベンゼン/アセトン(4:1)で溶出し、
10mlずつ分画した。活性画分(No.23〜39)を集め
て減圧下で濃縮することにより、油状物質150mg
を得た。
油状物質150mgは1.5mlアセトニトリルに溶か
し、15回に分けて高速液体クロマトグラフイー
(カラム、山村化学研究所製YMC A−324;展開
溶媒65%アセトニトリル水,流速3ml/mi,検
出 UV210nm;保持時間9.8分)を行なつた。こ
の活性分画を減圧下で濃縮乾固することにより、
白色粉末39mgを単離した。[Table] Selected culture medium
() Physiological properties (1) Production of melanin pigment (a) Tyrosine agar negative (b) Peptone/yeast iron agar negative (c) Glucose/beptone/gelatin medium (puncture (21-23℃) negative (d) Tryptone・Yeast liquid negative (2) Tyrosinase reaction negative (3) Hydrogen sulfide production negative (4) Nitrate reduction positive (5) Liquefaction of gelatin (21-23℃) (Glucose/peptone/gelatin medium) Negative (6) Starch Hydrolysis of skim milk Positive (7) Coagulation of skim milk (37℃) Negative (8) Peptonization of skim milk (37℃) Positive (9) Growth temperature range 15-45℃ (10) Availability of carbon source (Pleadam Codolive agar medium) Used: D-glycose, L-arabinose, D-xylose, raffinose, melibiose, D-mannitol, D-fructose, L-rhamnose, i-inositol, sucrose (11) Degradation of cellulose Negative () cells The chemical composition of diaminopimelic acid is the LL type, and arabinose and galactose were found in the sugar analysis of the whole bacterial cell.The mycological properties of this bacterium can be summarized as follows.The cell wall composition is LL. - Contains diaminopimelic acid. Morphologically, it forms a spiral spore chain, and the surface of the spore is hair-like. As for its cultural properties, the vegetative hyphae exhibit a bumpy or light ivory color. , the aerial mycelium exhibits a brownish gray color. It does not produce soluble pigments. Based on these results, this fungus belongs to the genus Streptomyces, and T.G. Pridham (TG
Pridham) and H.D. Tresner (HD
Tresner) classification [Bergeys Manual
Bergey's Manual of Determinative Bacteriology
Bacteriology) 8th edition, pages 748-829, 1974]
It is considered to be a bacterial species belonging to the Gray series. Mutant strains of the above-mentioned strains can also be used in the method of the invention. As a medium, a carbon source suitable for culturing actinomycetes,
Synthetic or natural media containing moderate amounts of nitrogen sources, minerals, and optionally other nutrients can be used. The carbon source and nitrogen source used in the culture medium may be any type as long as they are available to the strain used.
That is, carbon sources include, for example, glucose, glycerol, fructose, maltose,
Various carbohydrates can be used, such as mannite, xylose, galactose, ribose, starch or its hydrolysates. Its concentration is usually
0.1 to 5% (calculated as glucose) is preferable. Also,
Various organic acids such as gluconic acid, pyruvic acid, lactic acid, and acetic acid, various amino acids such as glycine, glutamic acid, and alanine, alcohols such as methanol and ethanol, and various non-aromatic hydrocarbons such as normal paraffin, Various vegetable or animal fats and oils can also be used. Nitrogen sources include ammonium salts of various inorganic or organic acids such as ammonia, ammonium chloride, ammonium phosphate, ammonium sulfate, ammonium nitrate, urea, peptone, NZ-amine, meat extract, yeast extract, dried yeast, corn steep liquor, Nitrogen-containing organic substances such as casein hydrolyzate, fat meal or its digested product, soybean flour or its digested product, defatted soybean or its digested product, pupa hydrolysate, and various amino acids such as glycine, glutamic acid, and alanine can be used. It is. As inorganic substances, various phosphates, magnesium sulfate, common salt, etc., and trace amounts of heavy metal salts are used. Furthermore, when using a mutant strain that exhibits auxotrophy, it is of course necessary to add a substance to the medium that satisfies its nutritional requirements; however, when using a medium containing natural substances, There are cases where no particular addition is required. Fermentation is carried out under aerobic conditions such as shaking culture or submerged culture with aeration and stirring. The culture temperature is usually 20-40°C. The culture period is usually 1 to 8 days, and the antibiotic SK-1071 is produced and accumulated inside and outside the bacterial cells. After culturing, antibiotic SK-1071 was added to the culture.
For example, collect it using the following method. The culture is separated into a liquid and a precipitate by centrifugation. It is extracted from the liquid by adsorbing it onto activated carbon, porous synthetic polymer resin, ion exchange resin, etc. and eluting it. The precipitate is extracted with an organic solvent such as ethyl acetate, n-butanol, or aqueous acetone.
By appropriately concentrating the extract to dryness, SK-
1071 crude material is obtained. The crude substance is further purified by appropriately combining known methods commonly used in the purification of fat-soluble substances, such as concentration methods such as silica gel column chromatography. By concentrating and drying the active fraction obtained by these purification methods, powder of antibiotic SK-1071 can be obtained. In the present invention, the antibiotic SK-1071 was detected and quantified using silica gel thin layer chromatography (Silica gel 60F 254 manufactured by Merck & Co., Ltd., thickness 0.2 nm, developing solvent benzene/acetone = 3:1, antibiotic
SK-1071 Rf value 0.40) and Clostridium perfringens (Clostridium perfringens)
A biological assay using ATCC 3624 was used. (Effect of the invention) As mentioned above, antibiotic SK-1071 has low toxicity;
Mainly active against anaerobic bacteria. Therefore,
This substance is expected to be used as a therapeutic or preventive agent for microbial infections in humans and animals. (Example) Next, an example of the antibiotic SK-1071 of the present invention will be shown, but this example is merely an example and does not limit the present invention. A platinum loop from a slant culture of Actinomycetes strain SK-1071 (Feikoken No. 8107) was added to 100 ml of seed medium (glucose 0.1%, starch 2.4%, peptone 0.3%, meat extract 0.3%, yeast extract 0.5%, Calcium carbonate 0.4
%) into a 500 ml Sakaguchi flask,
A seed culture was obtained by culturing with shaking at 27°C for 2 days. Add 400ml of this seed culture to 40ml of production medium (glucose 0.1%,
Starch 2.4%, peptone 0.3%, meat extract 0.3%,
Yeast extract 0.5%, calcium carbonate 0.4%, ferrous sulfate heptahydrate 1mg/, manganese chloride tetrahydrate 1mg/
, zinc sulfate heptahydrate 1 mg/, copper sulfate pentahydrate 1
mg/, cobalt chloride dihydrate 1 mg/30
The vaccine was divided into two separate units and 27
Culture with aeration at ℃ for 3 days (aeration rate 10/mm, stirring
250rpm). The culture solution 40 is centrifuged using a shear press type centrifuge to separate the bacterial cells and the culture supernatant. 2.5 g of 90% acetone solution was added to the bacterial cells and stirred to perform re-extraction. After concentrating this acetone solution under reduced pressure to remove acetone, it was combined with culture supernatant 18, and the pH was adjusted with hydrochloric acid.
Adjusted to 4. Add this to 650ml of Daikaiion Hp−
After passing through a column packed with 20% acetone, it was eluted with 70% acetone water and fractionated into individual fractions. Active fraction (No. 1~
3) was collected and concentrated under reduced pressure to remove acetone, the pH was adjusted to 3 with hydrochloric acid, and the mixture was extracted twice with ethyl acetate. The extract was concentrated to dryness under reduced pressure to obtain 840 mg of a tar-like substance. 840 mg of tar-like substance was dissolved in methanol, mixed with Celite, and then concentrated to dryness. This powder is 3
Silica gel (40 g, manufactured by Merck, pre-suspended in benzene)
Art.9385) was added to the top of the column packed. The column was eluted with benzene/acetone (4:1);
It was fractionated into 10 ml portions. By collecting the active fractions (No. 23-39) and concentrating under reduced pressure, 150 mg of oily substance was obtained.
I got it. 150 mg of the oily substance was dissolved in 1.5 ml acetonitrile, and divided into 15 times, high performance liquid chromatography (column, YMC A-324 manufactured by Yamamura Kagaku Kenkyusho; developing solvent 65% acetonitrile water, flow rate 3 ml/mi, detection UV 210 nm; retention time 9.8 minutes). By concentrating this active fraction to dryness under reduced pressure,
39 mg of white powder was isolated.
第1図は抗生物質SK−1071の紫外線吸収スペ
クトル(50%アセトニトリル水溶液中の測定)、
第2図は赤外線吸収スペクトル(KBr法)、第3
図はプロトン核磁気共嗚スペクトル(重クロロホ
ルム中で測定)、第4図はC−13核磁気共嗚スペ
クトル(重アセトン中で測定)を示す。
Figure 1 shows the ultraviolet absorption spectrum of antibiotic SK-1071 (measured in 50% acetonitrile aqueous solution).
Figure 2 is an infrared absorption spectrum (KBr method), Figure 3 is
The figure shows the proton nuclear magnetic resonance spectrum (measured in deuterated chloroform), and FIG. 4 shows the C-13 nuclear magnetic resonance spectrum (measured in deuterated acetone).
Claims (1)
で表される抗生物質SK−1071。 比旋光度:〔α〕18 D−0.1゜(C=1、アセトニト
リル) 紫外線吸収スペクトル:λCH 3 CN naxnm(ε)277
(6170)、350(4660)に吸収帯を有する。 赤外線吸収スペクトル:3400,1760,1740,
1710,1640,1600cm-1に吸収帯を有する。 C−13核磁気共嗚スペクトル:重アセトン中
のケミカルシフト ppm172.3(s),157.5
(d),144.0(s),139.5(s),135.3(s),
131.6(d),125.7(d),123.4(d),98.4(d)
,
88.9(d),79.5(d),76.8(s),74.3(d),73
.6
(t),69.7(d),67.4(d),66.3(d),63.3
(t),61.0(q),59.6(q),46.5(d),39.6
(d),38.3(t),38.0(d),34.5(t),33.5
(t),30.3(d),19.8(t),15.9(q) s:singlet,d:doublet,t:triplet, q:qultet 2 下記の理化学的性質を有し、分子式
C32H38O13で表される抗生物質SK−1071を生産
する能力を有するストレプトミセス属に属する微
生物を培地に好気的に培養し、該抗生物質SK−
1071を生産蓄積させ、これを採取することを特徴
とする抗生物質SK−1071の製造法。 比旋光度:〔α〕18 D−0.1゜(C=1、アセトニト
リル) 紫外線吸収スペクトル:λCH 3 CN naxnm(ε)277
(6170)、350(4660)に吸収帯を有する。 赤外線吸収スペクトル:3400,1760,1740,
1710,1640,1600cm-1に吸収帯を有する。 C−13核磁気共嗚スペクトル:重アセトン中
のケミカルシフト ppm172.3(s),157.5
(d),144.0(s),139.5(s),135.3(s),
131.6(d),125.7(d),123.4(d),98.4(d)
,
88.9(d),79.5(d),76.8(s),74.3(d),73
.6
(t),69.7(d),67.4(d),66.3(d),65.3
(t),61.0(q),59.6(q),46.5(d),39.6
(d),38.3(t),38.0(d),34.5(t),33.5
(t),30.3(d),19.8(t),15.9(q) s:singlet,d:doublet,t:triplet, e:qultet[Claims] 1. Having the following physical and chemical properties and having a molecular formula of C 32 H 38 O 13
Antibiotic SK-1071 represented by. Specific optical rotation: [α] 18 D −0.1° (C=1, acetonitrile) Ultraviolet absorption spectrum: λ CH 3 CN nax nm (ε) 277
It has absorption bands at (6170) and 350 (4660). Infrared absorption spectrum: 3400, 1760, 1740,
It has absorption bands at 1710, 1640, and 1600 cm -1 . C-13 nuclear magnetic resonance spectrum: chemical shift in heavy acetone ppm 172.3 (s), 157.5
(d), 144.0 (s), 139.5 (s), 135.3 (s),
131.6(d), 125.7(d), 123.4(d), 98.4(d)
,
88.9(d), 79.5(d), 76.8(s), 74.3(d), 73
.6
(t), 69.7(d), 67.4(d), 66.3(d), 63.3
(t), 61.0 (q), 59.6 (q), 46.5 (d), 39.6
(d), 38.3 (t), 38.0 (d), 34.5 (t), 33.5
(t), 30.3 (d), 19.8 (t), 15.9 (q) s: singlet, d: doublet, t: triplet, q: qultet 2 Has the following physical and chemical properties and has a molecular formula
A microorganism belonging to the genus Streptomyces that has the ability to produce the antibiotic SK-1071 represented by C 32 H 38 O 13 is cultured aerobically in a medium, and the antibiotic SK-1071 is grown in a medium.
A method for producing antibiotic SK-1071, which comprises producing and accumulating 1071 and collecting it. Specific optical rotation: [α] 18 D −0.1° (C=1, acetonitrile) Ultraviolet absorption spectrum: λ CH 3 CN nax nm (ε) 277
It has absorption bands at (6170) and 350 (4660). Infrared absorption spectrum: 3400, 1760, 1740,
It has absorption bands at 1710, 1640, and 1600 cm -1 . C-13 nuclear magnetic resonance spectrum: chemical shift in heavy acetone ppm 172.3 (s), 157.5
(d), 144.0 (s), 139.5 (s), 135.3 (s),
131.6(d), 125.7(d), 123.4(d), 98.4(d)
,
88.9(d), 79.5(d), 76.8(s), 74.3(d), 73
.6
(t), 69.7(d), 67.4(d), 66.3(d), 65.3
(t), 61.0 (q), 59.6 (q), 46.5 (d), 39.6
(d), 38.3 (t), 38.0 (d), 34.5 (t), 33.5
(t), 30.3 (d), 19.8 (t), 15.9 (q) s: singlet, d: doublet, t: triplet, e: qultet
Priority Applications (1)
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---|---|---|---|
JP60108427A JPS61268187A (en) | 1985-05-22 | 1985-05-22 | Novel antibiotic substance sk-1071 and production thereof |
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Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60108427A JPS61268187A (en) | 1985-05-22 | 1985-05-22 | Novel antibiotic substance sk-1071 and production thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS61268187A JPS61268187A (en) | 1986-11-27 |
JPH0468319B2 true JPH0468319B2 (en) | 1992-11-02 |
Family
ID=14484493
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JP60108427A Granted JPS61268187A (en) | 1985-05-22 | 1985-05-22 | Novel antibiotic substance sk-1071 and production thereof |
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-
1985
- 1985-05-22 JP JP60108427A patent/JPS61268187A/en active Granted
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