CN100366729C - 产生5′-黄苷酸的微生物 - Google Patents
产生5′-黄苷酸的微生物 Download PDFInfo
- Publication number
- CN100366729C CN100366729C CNB2003801019452A CN200380101945A CN100366729C CN 100366729 C CN100366729 C CN 100366729C CN B2003801019452 A CNB2003801019452 A CN B2003801019452A CN 200380101945 A CN200380101945 A CN 200380101945A CN 100366729 C CN100366729 C CN 100366729C
- Authority
- CN
- China
- Prior art keywords
- kccm
- xanthylic acid
- xmp
- cjxol
- corynebacterium ammoniagenes
- 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
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- DCTLYFZHFGENCW-UUOKFMHZSA-N 5'-xanthylic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 DCTLYFZHFGENCW-UUOKFMHZSA-N 0.000 title claims abstract description 50
- 244000005700 microbiome Species 0.000 title description 12
- 238000000034 method Methods 0.000 claims abstract description 24
- MNULEGDCPYONBU-WMBHJXFZSA-N (1r,4s,5e,5'r,6'r,7e,10s,11r,12s,14r,15s,16s,18r,19s,20r,21e,25s,26r,27s,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trio Polymers O([C@@H]1CC[C@@H](/C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)O[C@H]([C@H]2C)[C@H]1C)CC)[C@]12CC[C@@H](C)[C@@H](C[C@H](C)O)O1 MNULEGDCPYONBU-WMBHJXFZSA-N 0.000 claims abstract description 12
- MNULEGDCPYONBU-DJRUDOHVSA-N (1s,4r,5z,5'r,6'r,7e,10s,11r,12s,14r,15s,18r,19r,20s,21e,26r,27s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers O([C@H]1CC[C@H](\C=C/C=C/C[C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@H](C)[C@@H](O)C(C)C(=O)[C@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)OC([C@H]2C)C1C)CC)[C@]12CC[C@@H](C)[C@@H](CC(C)O)O1 MNULEGDCPYONBU-DJRUDOHVSA-N 0.000 claims abstract description 12
- MNULEGDCPYONBU-YNZHUHFTSA-N (4Z,18Z,20Z)-22-ethyl-7,11,14,15-tetrahydroxy-6'-(2-hydroxypropyl)-5',6,8,10,12,14,16,28,29-nonamethylspiro[2,26-dioxabicyclo[23.3.1]nonacosa-4,18,20-triene-27,2'-oxane]-3,9,13-trione Polymers CC1C(C2C)OC(=O)\C=C/C(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)C\C=C/C=C\C(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-YNZHUHFTSA-N 0.000 claims abstract description 12
- MNULEGDCPYONBU-VVXVDZGXSA-N (5e,5'r,7e,10s,11r,12s,14s,15r,16r,18r,19s,20r,21e,26r,29s)-4-ethyl-11,12,15,19-tetrahydroxy-6'-[(2s)-2-hydroxypropyl]-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers C([C@H](C)[C@@H](O)[C@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@H](C)/C=C/C(=O)OC([C@H]1C)[C@H]2C)\C=C\C=C\C(CC)CCC2OC21CC[C@@H](C)C(C[C@H](C)O)O2 MNULEGDCPYONBU-VVXVDZGXSA-N 0.000 claims abstract description 12
- MNULEGDCPYONBU-UHFFFAOYSA-N 4-ethyl-11,12,15,19-tetrahydroxy-6'-(2-hydroxypropyl)-5',10,12,14,16,18,20,26,29-nonamethylspiro[24,28-dioxabicyclo[23.3.1]nonacosa-5,7,21-triene-27,2'-oxane]-13,17,23-trione Polymers CC1C(C2C)OC(=O)C=CC(C)C(O)C(C)C(=O)C(C)C(O)C(C)C(=O)C(C)(O)C(O)C(C)CC=CC=CC(CC)CCC2OC21CCC(C)C(CC(C)O)O2 MNULEGDCPYONBU-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229930191479 oligomycin Natural products 0.000 claims abstract description 12
- MNULEGDCPYONBU-AWJDAWNUSA-N oligomycin A Polymers O([C@H]1CC[C@H](/C=C/C=C/C[C@@H](C)[C@H](O)[C@@](C)(O)C(=O)[C@@H](C)[C@H](O)[C@@H](C)C(=O)[C@@H](C)[C@H](O)[C@@H](C)/C=C/C(=O)O[C@@H]([C@@H]2C)[C@@H]1C)CC)[C@@]12CC[C@H](C)[C@H](C[C@@H](C)O)O1 MNULEGDCPYONBU-AWJDAWNUSA-N 0.000 claims abstract description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 32
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 16
- 229910021529 ammonia Inorganic materials 0.000 claims description 16
- 238000000855 fermentation Methods 0.000 abstract description 17
- 230000004151 fermentation Effects 0.000 abstract description 17
- 239000001963 growth medium Substances 0.000 abstract description 10
- 241000186145 Corynebacterium ammoniagenes Species 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 6
- 230000000241 respiratory effect Effects 0.000 abstract description 4
- 230000035772 mutation Effects 0.000 abstract description 3
- VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 abstract 1
- 230000005855 radiation Effects 0.000 abstract 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 10
- 239000011782 vitamin Substances 0.000 description 9
- 229930003231 vitamin Natural products 0.000 description 9
- 235000013343 vitamin Nutrition 0.000 description 9
- 229940088594 vitamin Drugs 0.000 description 9
- 150000003722 vitamin derivatives Chemical class 0.000 description 9
- 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 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000011218 seed culture Methods 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000011081 inoculation Methods 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- 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 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 229930003756 Vitamin B7 Natural products 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 239000011790 ferrous sulphate Substances 0.000 description 4
- 235000003891 ferrous sulphate Nutrition 0.000 description 4
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 4
- 235000013928 guanylic acid Nutrition 0.000 description 4
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 4
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 4
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 239000011735 vitamin B7 Substances 0.000 description 4
- 235000011912 vitamin B7 Nutrition 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229910000365 copper sulfate Inorganic materials 0.000 description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 3
- 239000004226 guanylic acid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000008929 regeneration Effects 0.000 description 3
- 238000011069 regeneration method Methods 0.000 description 3
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 239000013530 defoamer Substances 0.000 description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 239000012499 inoculation medium Substances 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000010627 oxidative phosphorylation Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940047022 zinc sulfate 10 mg Drugs 0.000 description 2
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical class [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
- UBORTCNDUKBEOP-UHFFFAOYSA-N L-xanthosine Natural products OC1C(O)C(CO)OC1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UHFFFAOYSA-N 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- UBORTCNDUKBEOP-HAVMAKPUSA-N Xanthosine Natural products O[C@@H]1[C@H](O)[C@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-HAVMAKPUSA-N 0.000 description 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940098081 copper sulfate 0.8 mg Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000000487 histidyl group Chemical class [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000008774 maternal effect Effects 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229930010796 primary metabolite Natural products 0.000 description 1
- 239000002213 purine nucleotide Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- UBORTCNDUKBEOP-UUOKFMHZSA-N xanthosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NC(=O)NC2=O)=C2N=C1 UBORTCNDUKBEOP-UUOKFMHZSA-N 0.000 description 1
- 239000012138 yeast extract 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
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229940079232 zinc sulfate 15 mg Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/30—Nucleotides
- C12P19/32—Nucleotides having a condensed ring system containing a six-membered ring having two N-atoms in the same ring, e.g. purine nucleotides, nicotineamide-adenine dinucleotide
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
- C12N1/205—Bacterial isolates
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
- C12P19/28—N-glycosides
- C12P19/38—Nucleosides
- C12P19/40—Nucleosides having a condensed ring system containing a six-membered ring having two nitrogen atoms in the same ring, e.g. purine nucleosides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
- C12R2001/15—Corynebacterium
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- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicinal Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
本发明涉及产生5′-黄苷酸的产氨棒杆菌CJXOL 0201 KCCM10447。更特别地，本发明涉及产氨棒杆菌CJXOL 0201 KCCM10447，其是一种具有寡霉素抗性的产氨棒杆菌KCCM 10340的突变株。为了获得具有增强的呼吸活性的突变株，本发明采用产氨棒杆菌KCCM 10340作为母株，并且根据普通程序，利用紫外射线和突变诱变剂如N-甲基-N′-硝基-正-亚硝基胍(NTG)对其进行处理。因此，本发明的产氨棒杆菌CJXOL 0201 KCCM 10447使得在相同的发酵周期提高ATP再生活性成为可能，并且能够在高产率和高浓度比率下在培养基中积聚5′-黄苷酸。
Description
技术领域
本发明涉及一种产生5′-黄苷酸的微生物。更具体地，本发明涉及一种产氨棒杆菌KCCM 10340的突变株，其对于抑制ATP合成酶活性和氧化磷酸化过程的寡霉素具有抗性，为了增强呼吸活性，使得在相同的发酵周期提高ATP的再生活性以及在高产率和高浓度比率下在培养基中积聚5′-黄苷酸成为可能。
背景技术
5′-黄苷酸是一种在核酸生物合成过程中的中间产物，其在生理学上对于动物体和植物体是很重要的，可用于食品、医疗用品以及其他不同领域中。本发明涉及一种具有寡霉素抗性的突变株，该突变株是从已知的产氨棒杆菌(Corynebacterium ammoniagenes)KCCM 10340菌株而获得的，通过直接发酵法在高产率和高浓度比率下生产5′-黄苷酸。
5′-黄苷酸是一种嘌呤核苷酸生物合成过程中的中间产物，并且是用于生产5′-鸟苷酸的重要原材料。一种广泛使用的用于生产精细而高质量的5′-鸟苷酸的方法是微生物发酵法，该方法首先生产5′-黄苷酸并将其酶转化成5′-鸟苷酸，因此，生产相应量的5′-黄苷酸对于生产5′-鸟苷酸是必需的。传统的生产5′-黄苷酸的方法是化学合成(化能合成)法：将酵母菌中的核糖核酸分解，结果产生脱氨基的5′-鸟苷酸，包括以下几种方法：在发酵培养基中加入黄嘌呤作为前体材料的发酵方法；利用微生物突变株的发酵方法；加入抗生素材料的方法(JP 1477/42和JP 20390/44)；以及加入表面活性剂的方法(JP 3825/42和JP 3838/42)等等。在这些方法中，通过微生物突变株的5′-黄苷酸的直接发酵法在产业化方面有着相当大的优势。因此，本申请发明人通过使产氨棒杆菌KCCM 10340现有的特性改变(modifying)为以高产率产生5′-黄苷酸的特性而得到了一种具有提高的5′-黄苷酸生产率的突变株。
大部分微生物达到一定条件，当在恒定的条件下培养时其体积不再增加，尤其是，微生物产生的初级代谢产物(即生长依靠型产物)的浓度不会再增加。这主要是由于有限的溶解氧供应而引起的。为了除去有限的溶解氧供应，可以使用增强通风条件和搅拌条件的方法，但是在实际生产中还存在技术上和经济上的制约。为了在有限的溶解氧供应条件下，通过提高微生物的体积和各种生理活性来克服此局限性并提高5′-黄苷酸的产率和浓度，本发明发明人认为：在同样的溶解氧条件下，提高微生物的呼吸活性和ATP再生活性的方法是有效的。因此，发明人研究了对各种呼吸抑制剂具有抗性的微生物菌株，并且发现对寡霉素具有抗性的突变株在这些微生物菌株中是最有效的，其可以在高产率和高浓度比率条件下通过直接发酵法来生产5′-黄苷酸，并且在本发明中实现了该目的。
发明内容
本发明涉及产氨棒杆菌CJXOL 0201(KCCM-10447)，其是产生5′-黄苷酸的产氨棒杆菌KCCM 103040的一种突变株。CJXOL0201是根据普通程序，通过利用紫外射线和突变诱变剂如N-甲基-N′-硝基-正-亚硝基胍(NTG)处理产氨棒杆菌KCCM 10340，并且从这些能够在加入不同浓度水平的寡霉素(1，2，5，10，20，50mg/L)的培养基(葡萄糖20g/L，磷酸二氢钾1g/L，磷酸氢二钾1g/L，尿素2g/L，硫酸铵3g/L，硫酸镁1g/L，氯化钙100mg/L，硫酸亚铁20mg/L，硫酸锰10mg/L，硫酸锌10mg/L，生物素30μg/L，盐酸硫胺素0.1mg/L，硫酸铜0.8mg/L，腺嘌呤20mg/L，鸟嘌呤20mg/L，pH7.2)中生长的菌株中选择而获得的一种突变株。在该程序中，将0～50mg/L的寡霉素加入到培养基中，并且显示出高达20mg/L的寡霉素抗性，但是当浓度水平高于20mg/L时，则没有观察到任何生长。将能够在20mg/L寡霉素中生长的菌株分离出来，并命名为CJXOL 0201，于2002年11月21日将其保藏在布达佩斯条约下的韩国微生物培养中心，保藏编号为KCCM 10447。
本发明的新颖的突变株CJXOL 0201的生物化学特性如以下的表1所示。根据表1，本发明的微生物能够在加入了10mg/L的寡霉素的培养基中生长。该培养基在30℃下发酵5天。
表1
| 菌株 | 寡霉素浓度(mg/L) | ||||||
| 0 | 5 | 10 | 20 | 30 | 40 | 50 | |
| KCCM10340 | +++ | ++ | + | - | - | - | - |
| CJXOL0201 | +++ | +++ | ++ | ++ | + | - | - |
+：生长；-：不生长
具体实施方式
实施例1
所使用的菌株：产氨棒杆菌KCCM 10340，产氨棒杆菌CJXOL0201
接种培养基：葡萄糖30g/L，蛋白胨15g/L，酵母提取物15g/L，氯化钠2.5g/L，尿素3g/L，腺嘌呤150mg/L，鸟嘌呤150mg/L，pH7.2
发酵培养基：(1)A培养基：葡萄糖60g/L，硫酸镁10g/L，硫酸亚铁20mg/L，硫酸锌10mg/L，硫酸锰10mg/L，腺嘌呤30mg/L，鸟嘌呤30mg/L，生物素100μg/L，硫酸铜1mg/L，盐酸硫胺素5mg/L，氯化钙10mg/L，pH7.2
(2)B培养基：磷酸二氢钾10g/L，磷酸氢二钾10g/L，尿素7g/L，硫酸铵5g/L
发酵方法：将5mL的接种培养基倒入直径为18mm的试管，并且根据常见方法在压力下灭菌。灭菌之后，分别将产氨棒杆菌KCCM 10340和产氨棒杆菌CJXOL 0201接种，并且在180rpm、30℃下摇床培养18小时。将该产物用作种子培养物。然后，作为发酵培养基，将A培养基和B培养基按照常规方法分别在压力下灭菌，将29mL的A培养基和10mL的B培养基分别倒入用于摇动的已灭菌的500毫升(mL)锥形烧瓶中，并且将1mL的上述种子培养物接种到培养基中，在200rpm、30℃下发酵90小时。在发酵完成之后，显示在KCCM 10340中的5′-黄苷酸的积聚量为23.0g/L，而在CJXOL 0201中的5′-黄苷酸的积聚量为26.5g/L。(5′-黄苷酸的积聚浓度是以5′-黄苷酸钠·7H2O给出的)。
实施例2
所使用的菌株：与实施例1相同
一次种子培养基：与实施例1的种子培养基相同
二次种子培养基：葡萄糖60g/L，磷酸二氢钾2g/L，磷酸氢二钾2g/L，硫酸镁1g/L，硫酸亚铁22mg/L，硫酸锌15mg/L，硫酸锰10mg/L，硫酸铜1mg/L，氯化钙100mg/L，生物素150μg/L，腺嘌呤150mg/L，鸟嘌呤150mg/L，盐酸硫胺素5mg/L，消泡剂0.6mL/L，pH7.2
发酵培养基：葡萄糖151g/L，磷酸32g/L，氢氧化钾25g/L，腺嘌呤198mg/L，鸟嘌呤119mg/L，硫酸亚铁60mg/L，硫酸锌42mg/L，硫酸锰15mg/L，硫酸铜2.4mg/L，丙氨酸盐22mg/L，NCA7.5mg/L，生物素0.4mg/L，硫酸镁15g/l，胱氨酸盐30mg/L，组氨酸盐30mg/L，氯化钙149mg/L，盐酸硫胺素15mg/L，消泡剂0.7mL/L，CSL 27mL/L，金枪鱼提取物6g/L，pH 7.3
一次接种培养：将50mL的一次种子培养基倒入500mL用于摇动的锥形瓶中，并且在121℃、压力下灭菌20分钟。冷却以后，将产氨棒杆菌KCCM 10340和产氨棒杆菌CJXOL 0201分别进行接种，并且在180rpm、30℃下摇床培养24小时。
二次接种培养：将二次种子培养基倒入5L的试验发酵浴中(每个为2L)，在121℃、加压下灭菌10分钟。冷却以后，将50mL的上述一次种子培养基接种，并且在供气速率为0.5vvm，在900rpm、31℃下培养24小时。在培养过程中，培养基的pH值通过氨溶液来调节，使pH值保持在7.3。
发酵方法：将发酵培养基倒入30L的试验发酵浴中(每个为8L)，并在121℃、压力下灭菌20分钟。冷却以后，将上述的二次种子培养基(每个1.5L)接种，并在空气供应速率为1vvm，在400rpm及33℃下培养。在培养过程中，只要当残余糖的水平下降至低于1％时，就加入已灭菌的葡萄糖，并使在发酵培养基中的总糖水平保持在30％。在培养过程中，培养基的pH水平通过氨溶液来调节，并使之保持在7.3，并且该过程进行90小时。在发酵完成之后，显示在KCCM 10340的培养基中的5′-黄苷酸积聚量为137.2g/L，而在CJXOL 0201的培养基中的5′-黄苷酸积聚量为148.4g/L。(积聚5′-黄苷酸的浓度是以5′-黄苷酸钠·7H2O给出的)。
工业实用性
本发明适合的产氨棒杆菌KCCM 10340作为母株，并且根据普通程序用紫外射线或者诱变剂如N-甲基-N′-硝基-正-亚硝基胍(NTG)对其进行处理。KCCM 10340菌株对于渗透压具有抵抗力，该渗透压是由在培养过程中积聚的高浓度的5′-黄苷酸、高浓度的葡萄糖以及在培养基中所加入的各种碳源引起的，其导致菌体外部的高渗透压，抑制产生5′-黄苷酸细胞的正常生理活动并减少5′-黄苷酸的产生。为了获得具有增强的抗渗透压特性和增强的呼吸活性的菌株，本发明对产氨棒杆菌KCCM 10340进行改变，并选择了对于抑制ATP合成酶活性和氧化磷酸化过程的寡霉素具有抗性的突变株，其使得可以提高ATP再生活性并在发酵的相同周期以高产率和高浓度比率在培养基中积聚5′-黄苷酸。
| 申请人或代理机构卷号YL03017PCT | 国际申请号PCT/KR2003/002703 |
涉及微生物或其他生物材料保藏的证明
(PCT条约13bis)
| A..以下证明涉及说明书第3页，第18-19行提及的微生物或其他生物材料的保藏 | |
| B.保藏证明 更多保藏见附页□ | |
| 保藏单位名称韩国微生物培养中心(KCCM) | |
| 保藏单位地址(包含邮政编码及国家)361-221，Yurim B/DHongje 1-dong，Seodaemun-gu120-091 Seoul(汉城)Republic of Korea(韩国) | |
| 保藏日期2002年11月21日 | 保藏编号KCCM-10447 |
| C.其它内容(如果没有则保留空白) 此信息接附页□ | |
| D.指定的国家，为该指定国家提供证明(如果本证明不适用于所有指定的国家) | |
| E.分别提交的证明(如果没有则保留空白) | |
| 下列证明将随后提交到国际局(详细说明该证明的一般内容，例如保藏编号) | |
| 受理局专用 | 国际局专用 |
| □此页与国际申请同时收到 | □此页由国际局在以下时间收到： |
| 经办人 | 经办人 |
PCT/RO/134表(1998年7月)
Claims (2)
1.具有寡霉素抗性并产生5′-黄苷酸的产氨棒杆菌CJXOL 0201，其保藏编号：KCCM10447。
2.一种通过利用权利要求1所述的产氨棒杆菌CJXOL 0201来生产5′-黄苷酸的方法，其保藏编号为KCCM 10447。
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| KR1020020078693 | 2002-12-11 | ||
| KR10-2002-0078693A KR100505925B1 (ko) | 2002-12-11 | 2002-12-11 | 5’-크산틸산을 생산하는 미생물 |
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| EP (1) | EP1570049A4 (zh) |
| JP (1) | JP4177334B2 (zh) |
| KR (1) | KR100505925B1 (zh) |
| CN (1) | CN100366729C (zh) |
| AU (1) | AU2003302756A1 (zh) |
| BR (2) | BRPI0314902B1 (zh) |
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| KR100588578B1 (ko) * | 2004-12-01 | 2006-06-14 | 씨제이 주식회사 | 5'-크산틸산 생성 미생물 및 이를 사용한 5'-크산틸산의생산 방법 |
| KR100959662B1 (ko) * | 2008-01-04 | 2010-05-26 | 씨제이제일제당 (주) | 이노신 생산능을 갖는 코리네박테리움속 미생물 및 이를이용한 이노신의 생산 방법 |
| KR101072708B1 (ko) * | 2008-12-17 | 2011-10-11 | 씨제이제일제당 (주) | ５＇－크산틸산 생산능이 향상된 미생물 및 이를 이용한 ５＇－크산틸산의 생산방법 |
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| EP0350970A1 (en) * | 1983-02-25 | 1990-01-17 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing L-glutamic acid by fermentation and mutant microorganisms for use therein |
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| US4438196A (en) * | 1982-09-28 | 1984-03-20 | Miles Laboratories, Inc. | Immobilization of biocatalysts on granular carbon |
| JP2000295996A (ja) * | 1999-02-08 | 2000-10-24 | Kyowa Hakko Kogyo Co Ltd | プリンヌクレオチドの製造法 |
| KR100344017B1 (ko) * | 2000-04-08 | 2002-07-20 | 제일제당주식회사 | 5'-크산틸산을 생산하는 미생물 |
| RU2209249C2 (ru) * | 2000-11-22 | 2003-07-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | Способ получения ксантозин-5'-монофосфата, штамм corynebacterium ammoniagenes - продуцент ксантозин-5'-монофосфата (варианты) |
| KR100402320B1 (ko) * | 2001-01-05 | 2003-10-22 | 씨제이 주식회사 | 5'-크산틸산을 고수율로 생산하는 미생물 코리네박테리움암모니아게네스 엔브이4-82-9 및 그를 이용한 5'-크산틸산생산방법 |
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| EP0350970A1 (en) * | 1983-02-25 | 1990-01-17 | Kyowa Hakko Kogyo Co., Ltd. | Process for producing L-glutamic acid by fermentation and mutant microorganisms for use therein |
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Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05004142A (es) | 2005-10-05 |
| KR20040051730A (ko) | 2004-06-19 |
| JP2006502740A (ja) | 2006-01-26 |
| US20060154346A1 (en) | 2006-07-13 |
| US7217558B2 (en) | 2007-05-15 |
| AU2003302756A1 (en) | 2004-06-30 |
| BR0314902A (pt) | 2005-08-02 |
| RU2005111595A (ru) | 2006-03-20 |
| WO2004053109A1 (en) | 2004-06-24 |
| CN1708581A (zh) | 2005-12-14 |
| EP1570049A4 (en) | 2006-05-10 |
| EP1570049A1 (en) | 2005-09-07 |
| JP4177334B2 (ja) | 2008-11-05 |
| RU2312140C2 (ru) | 2007-12-10 |
| KR100505925B1 (ko) | 2005-08-03 |
| BRPI0314902B1 (pt) | 2019-11-26 |
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