DE69937086T2 - Genetisch veränderte, L-Sorbose Reduktase defiziente Mutanten - Google Patents
Genetisch veränderte, L-Sorbose Reduktase defiziente Mutanten Download PDFInfo
- Publication number
- DE69937086T2 DE69937086T2 DE69937086T DE69937086T DE69937086T2 DE 69937086 T2 DE69937086 T2 DE 69937086T2 DE 69937086 T DE69937086 T DE 69937086T DE 69937086 T DE69937086 T DE 69937086T DE 69937086 T2 DE69937086 T2 DE 69937086T2
- Authority
- DE
- Germany
- Prior art keywords
- sorbose
- microorganism
- gene
- sorbose reductase
- genetically modified
- 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 - Fee Related
Links
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 title claims description 125
- 230000002950 deficient Effects 0.000 title claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 91
- 108090000854 Oxidoreductases Proteins 0.000 claims description 78
- 244000005700 microbiome Species 0.000 claims description 54
- 102000004316 Oxidoreductases Human genes 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 31
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 27
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 26
- 229960002920 sorbitol Drugs 0.000 claims description 26
- 239000012634 fragment Substances 0.000 claims description 25
- 108020004414 DNA Proteins 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 23
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 20
- 238000003780 insertion Methods 0.000 claims description 20
- 230000037431 insertion Effects 0.000 claims description 20
- 230000035772 mutation Effects 0.000 claims description 18
- 241000589236 Gluconobacter Species 0.000 claims description 17
- 230000004151 fermentation Effects 0.000 claims description 17
- 238000000855 fermentation Methods 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 14
- 241000589220 Acetobacter Species 0.000 claims description 13
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 10
- 229930003268 Vitamin C Natural products 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 235000019154 vitamin C Nutrition 0.000 claims description 10
- 239000011718 vitamin C Substances 0.000 claims description 10
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 8
- 238000007792 addition Methods 0.000 claims description 7
- 230000003115 biocidal effect Effects 0.000 claims description 7
- 238000012217 deletion Methods 0.000 claims description 7
- 230000037430 deletion Effects 0.000 claims description 7
- 230000014509 gene expression Effects 0.000 claims description 7
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 6
- 229920001184 polypeptide Polymers 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 230000004071 biological effect Effects 0.000 claims description 5
- 230000002068 genetic effect Effects 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 230000002452 interceptive effect Effects 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 102000040430 polynucleotide Human genes 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 238000002360 preparation method Methods 0.000 claims 3
- 241000589232 Gluconobacter oxydans Species 0.000 description 41
- 238000002703 mutagenesis Methods 0.000 description 27
- 231100000350 mutagenesis Toxicity 0.000 description 27
- 239000013598 vector Substances 0.000 description 26
- 239000013612 plasmid Substances 0.000 description 22
- 239000002609 medium Substances 0.000 description 18
- 239000003550 marker Substances 0.000 description 15
- 241000588724 Escherichia coli Species 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 125000003729 nucleotide group Chemical group 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- 238000009396 hybridization Methods 0.000 description 8
- 238000003752 polymerase chain reaction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 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 7
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 239000000600 sorbitol Substances 0.000 description 7
- 238000002105 Southern blotting Methods 0.000 description 6
- 238000010367 cloning Methods 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 238000002741 site-directed mutagenesis Methods 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 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 5
- 108700026244 Open Reading Frames Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000010276 construction Methods 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 229930027917 kanamycin Natural products 0.000 description 4
- 229960000318 kanamycin Drugs 0.000 description 4
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 4
- 229930182823 kanamycin A Natural products 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 239000013615 primer Substances 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 230000017105 transposition Effects 0.000 description 4
- 238000011144 upstream manufacturing Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010010144 Completed suicide Diseases 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 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 3
- 239000003155 DNA primer Substances 0.000 description 3
- 241000702191 Escherichia virus P1 Species 0.000 description 3
- 108020000290 Mannitol dehydrogenase Proteins 0.000 description 3
- 108700005075 Regulator Genes Proteins 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229940041514 candida albicans extract Drugs 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 239000013611 chromosomal DNA Substances 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 210000000172 cytosol Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000012138 yeast extract Substances 0.000 description 3
- JNRLEMMIVRBKJE-UHFFFAOYSA-N 4,4'-Methylenebis(N,N-dimethylaniline) Chemical compound C1=CC(N(C)C)=CC=C1CC1=CC=C(N(C)C)C=C1 JNRLEMMIVRBKJE-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
- 108020004705 Codon Proteins 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 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
- 101150027059 SR gene Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108010020764 Transposases Proteins 0.000 description 2
- 102000008579 Transposases Human genes 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000002962 chemical mutagen Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 101150066555 lacZ gene Proteins 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 230000002934 lysing effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- VBUYCZFBVCCYFD-NUNKFHFFSA-N 2-dehydro-L-idonic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)C(=O)C(O)=O VBUYCZFBVCCYFD-NUNKFHFFSA-N 0.000 description 1
- 244000283763 Acetobacter aceti Species 0.000 description 1
- 235000007847 Acetobacter aceti Nutrition 0.000 description 1
- 241000589212 Acetobacter pasteurianus Species 0.000 description 1
- 244000235858 Acetobacter xylinum Species 0.000 description 1
- 235000002837 Acetobacter xylinum Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- HEBKCHPVOIAQTA-NGQZWQHPSA-N D-Arabitol Natural products OC[C@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-NGQZWQHPSA-N 0.000 description 1
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
- VBUYCZFBVCCYFD-UHFFFAOYSA-N D-arabino-2-Hexulosonic acid Natural products OCC(O)C(O)C(O)C(=O)C(O)=O VBUYCZFBVCCYFD-UHFFFAOYSA-N 0.000 description 1
- 238000007900 DNA-DNA hybridization Methods 0.000 description 1
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 108010074122 Ferredoxins Proteins 0.000 description 1
- 241000032686 Gluconacetobacter liquefaciens Species 0.000 description 1
- 241001330169 Gluconobacter albidus Species 0.000 description 1
- 241001518248 Gluconobacter cerinus Species 0.000 description 1
- 241001631175 Gluconobacter roseus Species 0.000 description 1
- 241001216837 Gluconobacter sphaericus Species 0.000 description 1
- 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 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- PWGOWIIEVDAYTC-UHFFFAOYSA-N ICR-170 Chemical compound Cl.Cl.C1=C(OC)C=C2C(NCCCN(CCCl)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 PWGOWIIEVDAYTC-UHFFFAOYSA-N 0.000 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 241000589216 Komagataeibacter hansenii Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000006142 Luria-Bertani Agar Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 101100084022 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) lapA gene Proteins 0.000 description 1
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 241000191043 Rhodobacter sphaeroides Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010024649 Sorbose reductase Proteins 0.000 description 1
- 108010012306 Tn5 transposase Proteins 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 241000700605 Viruses Species 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
- GQXSDDHYUVYJCQ-NHRVJRKFSA-N [(3as,4as,8ar,8bs)-2,2,7,7-tetramethyl-4a,5,8a,8b-tetrahydro-[1,3]dioxolo[3,4]furo[1,3-d][1,3]dioxin-3a-yl]methanol Chemical compound O([C@H]12)C(C)(C)OC[C@@H]1O[C@]1(CO)[C@H]2OC(C)(C)O1 GQXSDDHYUVYJCQ-NHRVJRKFSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 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 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000012736 aqueous medium Substances 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
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 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
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000012262 fermentative production Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000012252 genetic analysis Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002972 pentoses Chemical class 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 101150009573 phoA gene Proteins 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000013337 sub-cultivation Methods 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- SPOMEWBVWWDQBC-UHFFFAOYSA-K tripotassium;dihydrogen phosphate;hydrogen phosphate Chemical compound [K+].[K+].[K+].OP(O)([O-])=O.OP([O-])([O-])=O SPOMEWBVWWDQBC-UHFFFAOYSA-K 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
Classifications
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/102—Mutagenizing nucleic acids
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/52—Genes encoding for enzymes or proenzymes
-
- 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
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
- C12P1/04—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using bacteria
-
- 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
- C12P19/02—Monosaccharides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98104546 | 1998-03-13 | ||
| EP98104546 | 1998-03-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69937086D1 DE69937086D1 (de) | 2007-10-25 |
| DE69937086T2 true DE69937086T2 (de) | 2008-06-12 |
Family
ID=8231579
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69937086T Expired - Fee Related DE69937086T2 (de) | 1998-03-13 | 1999-03-08 | Genetisch veränderte, L-Sorbose Reduktase defiziente Mutanten |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6664082B1 (enExample) |
| JP (1) | JP2000060576A (enExample) |
| KR (1) | KR100710948B1 (enExample) |
| CN (1) | CN1163593C (enExample) |
| AU (1) | AU2039099A (enExample) |
| BR (1) | BR9902010A (enExample) |
| CA (1) | CA2265239A1 (enExample) |
| DE (1) | DE69937086T2 (enExample) |
| ID (1) | ID23461A (enExample) |
| NO (1) | NO991197L (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080160588A1 (en) * | 2005-02-11 | 2008-07-03 | Bastian Chevreux | Alcohol Dehydrogenase Gene from Gluconobacter Oxydans |
| EP1859031A2 (en) * | 2005-02-11 | 2007-11-28 | DSMIP Assets B.V. | Gene sms 04 |
| WO2007028610A2 (en) * | 2005-09-09 | 2007-03-15 | Dsm Ip Assets B.V. | Novel gene gms 08 |
| WO2012104987A1 (ja) * | 2011-02-01 | 2012-08-09 | 国立大学法人福島大学 | 酵素及びその製造方法 |
| CN114507681B (zh) * | 2022-03-17 | 2023-08-22 | 乐山利源科技有限公司 | 一种山梨糖还原酶OpCR基因、突变体及编码蛋白和在制备玻色因中的应用 |
| EP4488376A1 (de) | 2023-07-07 | 2025-01-08 | Annikki GmbH | Verfahren zur herstellung einer wässerigen lösung enthaltend l-sorbose |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3537624A1 (de) * | 1985-10-23 | 1987-04-23 | Bayer Ag | Feinteilige isometrische hexaferritpigmente, verfahren zu ihrer herstellung und deren verwendung |
| EP0233050B1 (en) | 1986-02-11 | 1992-09-16 | Takeda Chemical Industries, Ltd. | Method for producing l-sorbose |
| EP0728840B1 (en) | 1995-02-27 | 2007-04-25 | DSM IP Assets B.V. | D-Sorbitol dehydrogenase |
-
1999
- 1999-03-08 DE DE69937086T patent/DE69937086T2/de not_active Expired - Fee Related
- 1999-03-11 AU AU20390/99A patent/AU2039099A/en not_active Abandoned
- 1999-03-11 US US09/266,320 patent/US6664082B1/en not_active Expired - Lifetime
- 1999-03-11 NO NO991197A patent/NO991197L/no not_active Application Discontinuation
- 1999-03-12 CA CA002265239A patent/CA2265239A1/en not_active Abandoned
- 1999-03-12 CN CNB991036875A patent/CN1163593C/zh not_active Expired - Fee Related
- 1999-03-12 KR KR1019990008359A patent/KR100710948B1/ko not_active Expired - Fee Related
- 1999-03-12 ID IDP990211D patent/ID23461A/id unknown
- 1999-03-12 BR BR9902010-6A patent/BR9902010A/pt not_active Application Discontinuation
- 1999-03-15 JP JP11068954A patent/JP2000060576A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| AU2039099A (en) | 1999-09-23 |
| BR9902010A (pt) | 2000-05-02 |
| CA2265239A1 (en) | 1999-09-13 |
| NO991197D0 (no) | 1999-03-11 |
| NO991197L (no) | 1999-09-14 |
| JP2000060576A (ja) | 2000-02-29 |
| KR19990077840A (ko) | 1999-10-25 |
| HK1021993A1 (en) | 2000-07-21 |
| KR100710948B1 (ko) | 2007-04-24 |
| DE69937086D1 (de) | 2007-10-25 |
| US6664082B1 (en) | 2003-12-16 |
| CN1229134A (zh) | 1999-09-22 |
| CN1163593C (zh) | 2004-08-25 |
| ID23461A (id) | 2000-04-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0334841B1 (de) | Microorganismen and plasmide für die 2,4-dichlorphenoxyessigsäure (2,4-d)-monooxigenase - bildung und verfahren zur herstellung dieser plasmide und stämme | |
| EP0796914B1 (de) | Alkohol-Dehydrogenase und deren Verwendung zur enzymatischen Herstellung chiraler Hydroxy-verbindungen | |
| DE69033616T3 (de) | Riboflavin überproduzierende Bakterienstämme | |
| EP0276832A2 (de) | Verfahren zur Herstellung von Ketogulonsäure | |
| DE69333546T2 (de) | Verbesserte enzyme zur herstellung von 2-keto-l-gulonsäure | |
| DE60028777T2 (de) | Verfahren zur herstellung von 1,3-propanediol durch einen rekombinanten microorganismus in abwesenheit von coenzym b12 | |
| DE68924761T2 (de) | Neue coenzym unabhängige l-sorbosone dehydrogenase. | |
| EP0798384A1 (de) | Biotechnologisches Verfahren zur Herstellung von Biotin | |
| EP0290768B1 (de) | Verfahren zur Herstellung von Glucosedehydrogenase aus Bacillus megaterium | |
| DE69937086T2 (de) | Genetisch veränderte, L-Sorbose Reduktase defiziente Mutanten | |
| EP0722500B1 (de) | Gene für den butyrobetain/crotonobetain-l-carnitin-stoffwechsel und ihre verwendung zur mikrobiologischen herstellung von l-carnitin | |
| DE69131015T2 (de) | Rekombinante zellen, die stark chromosomal-integrierte heterologe gene exprimieren | |
| DE69031803T2 (de) | Verfahren und nukleinsäuresequenzen zur expression des zellulose-synthase-operons | |
| DE69829240T2 (de) | Für temperaturstabile Diaphorase kodierendes Gen | |
| DE60316424T2 (de) | Beta-untereinheit von glucosedehydrogenase und diese kodierende dna | |
| EP0469523B1 (de) | Klonierung und Überexpression von Glucose-6-Phosphat-Dehydrogenase aus Leuconostoc dextranicus | |
| EP0543344B1 (de) | Mikroorganismen zur Stabilisierung von Plasmiden | |
| EP0955358B1 (en) | Genetically engineered L-sorbose reductase-deficient mutants | |
| Segura et al. | Anthracyclines: isolation of overproducing strains by the selection and genetic recombination of putative regulatory mutants of Streptomycespeucetius var. caesius | |
| DE19850242A1 (de) | Konstruktion von Produktionsstämmen für die Herstellung von substituierten Phenolen durch gezielte Inaktivierung von Genen des Eugenol- und Ferulasäure-Katabolismus | |
| DE69931176T2 (de) | Neue bacillus subtilis stämme für lebensmittelfermentierung | |
| DE3786578T2 (de) | Biotin-Synthetase kodierendes Gen und dessen Verwendung. | |
| DE69232114T2 (de) | Für ein Enzym mit flavinreduzierender und Nitroreduktase-Aktivität kodierendes Gen | |
| DE69233447T2 (de) | Biotin-Operon | |
| DE10220234B4 (de) | Verfahren sowie Mikroorganismen zur mikrobiellen Herstellung von Pyruvat aus Kohlenhydraten sowie Alkoholen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |