JP5960604B2 - カダベリンの生産のための方法及び組換え微生物 - Google Patents
カダベリンの生産のための方法及び組換え微生物 Download PDFInfo
- Publication number
- JP5960604B2 JP5960604B2 JP2012543730A JP2012543730A JP5960604B2 JP 5960604 B2 JP5960604 B2 JP 5960604B2 JP 2012543730 A JP2012543730 A JP 2012543730A JP 2012543730 A JP2012543730 A JP 2012543730A JP 5960604 B2 JP5960604 B2 JP 5960604B2
- Authority
- JP
- Japan
- Prior art keywords
- cadaverine
- activity
- lysine
- gene
- microorganism
- 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
- VHRGRCVQAFMJIZ-UHFFFAOYSA-N cadaverine Chemical compound NCCCCCN VHRGRCVQAFMJIZ-UHFFFAOYSA-N 0.000 title claims description 358
- 244000005700 microbiome Species 0.000 title claims description 159
- 238000004519 manufacturing process Methods 0.000 title claims description 72
- 230000000694 effects Effects 0.000 claims description 215
- 239000004472 Lysine Substances 0.000 claims description 126
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 122
- 108010048581 Lysine decarboxylase Proteins 0.000 claims description 106
- 230000014509 gene expression Effects 0.000 claims description 78
- 238000000034 method Methods 0.000 claims description 77
- 229920001184 polypeptide Polymers 0.000 claims description 64
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 64
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 64
- 150000001413 amino acids Chemical group 0.000 claims description 58
- 230000003834 intracellular effect Effects 0.000 claims description 39
- 239000001963 growth medium Substances 0.000 claims description 37
- 108010039491 Ricin Proteins 0.000 claims description 33
- 241000186226 Corynebacterium glutamicum Species 0.000 claims description 32
- RMOIHHAKNOFHOE-UHFFFAOYSA-N N-acetylcadaverine Chemical compound CC(=O)NCCCCCN RMOIHHAKNOFHOE-UHFFFAOYSA-N 0.000 claims description 29
- 230000008676 import Effects 0.000 claims description 29
- QZBYOYPROVGOGE-UHFFFAOYSA-N aminopropylcadaverine Chemical compound NCCCCCNCCCN QZBYOYPROVGOGE-UHFFFAOYSA-N 0.000 claims description 24
- 108010064711 Homoserine dehydrogenase Proteins 0.000 claims description 23
- 238000012217 deletion Methods 0.000 claims description 21
- 230000037430 deletion Effects 0.000 claims description 21
- 241000186216 Corynebacterium Species 0.000 claims description 17
- 230000015572 biosynthetic process Effects 0.000 claims description 11
- 102000008490 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Human genes 0.000 claims description 9
- 108010020504 2-Oxoglutarate 5-Dioxygenase Procollagen-Lysine Proteins 0.000 claims description 9
- 230000012010 growth Effects 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 4
- 230000015556 catabolic process Effects 0.000 claims description 3
- 230000006378 damage Effects 0.000 claims description 3
- 238000006731 degradation reaction Methods 0.000 claims description 3
- 230000003247 decreasing effect Effects 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 description 211
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 126
- 235000018977 lysine Nutrition 0.000 description 115
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 73
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 52
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 49
- 239000002609 medium Substances 0.000 description 48
- 239000000047 product Substances 0.000 description 44
- 210000004027 cell Anatomy 0.000 description 40
- 108020004414 DNA Proteins 0.000 description 37
- 241000588724 Escherichia coli Species 0.000 description 34
- 238000000855 fermentation Methods 0.000 description 33
- 230000004151 fermentation Effects 0.000 description 33
- 108090000084 Antiporters Proteins 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 32
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 32
- 102000003669 Antiporters Human genes 0.000 description 27
- 235000001014 amino acid Nutrition 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 27
- 102000004190 Enzymes Human genes 0.000 description 26
- 108090000790 Enzymes Proteins 0.000 description 26
- 229940088598 enzyme Drugs 0.000 description 26
- 230000035772 mutation Effects 0.000 description 26
- KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 26
- 229940024606 amino acid Drugs 0.000 description 25
- 108091028043 Nucleic acid sequence Proteins 0.000 description 24
- 230000002074 deregulated effect Effects 0.000 description 24
- 101150025220 sacB gene Proteins 0.000 description 21
- 101100309436 Streptococcus mutans serotype c (strain ATCC 700610 / UA159) ftf gene Proteins 0.000 description 20
- 238000013518 transcription Methods 0.000 description 20
- 230000035897 transcription Effects 0.000 description 20
- 108090000301 Membrane transport proteins Proteins 0.000 description 19
- 229940063673 spermidine Drugs 0.000 description 16
- 102000003939 Membrane transport proteins Human genes 0.000 description 15
- 230000001965 increasing effect Effects 0.000 description 15
- 101100398755 Escherichia coli (strain K12) ldcC gene Proteins 0.000 description 14
- 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 14
- 108020002494 acetyltransferase Proteins 0.000 description 14
- 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 14
- 239000013612 plasmid Substances 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 239000005700 Putrescine Substances 0.000 description 13
- 239000008103 glucose Substances 0.000 description 13
- 239000013598 vector Substances 0.000 description 13
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 12
- 101150007959 Lum gene Proteins 0.000 description 11
- 101100498625 Selenomonas ruminantium ldc gene Proteins 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 235000014469 Bacillus subtilis Nutrition 0.000 description 10
- 108090000489 Carboxy-Lyases Proteins 0.000 description 10
- 102000004031 Carboxy-Lyases Human genes 0.000 description 10
- 102000005421 acetyltransferase Human genes 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 150000007523 nucleic acids Chemical group 0.000 description 10
- 229930006000 Sucrose Natural products 0.000 description 9
- 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 9
- 238000010276 construction Methods 0.000 description 9
- 238000012258 culturing Methods 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 230000002708 enhancing effect Effects 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 230000001939 inductive effect Effects 0.000 description 9
- 101150044424 lysE gene Proteins 0.000 description 9
- 230000004060 metabolic process Effects 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- 239000005720 sucrose Substances 0.000 description 9
- 235000000346 sugar Nutrition 0.000 description 9
- 230000014616 translation Effects 0.000 description 9
- 108010055400 Aspartate kinase Proteins 0.000 description 8
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose 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)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 8
- 229930091371 Fructose Natural products 0.000 description 8
- 239000005715 Fructose Substances 0.000 description 8
- 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 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 108010076504 Protein Sorting Signals Proteins 0.000 description 8
- 210000000349 chromosome Anatomy 0.000 description 8
- 230000003831 deregulation Effects 0.000 description 8
- 239000003623 enhancer Substances 0.000 description 8
- 238000012807 shake-flask culturing Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000013519 translation Methods 0.000 description 8
- 102000053602 DNA Human genes 0.000 description 7
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 7
- 238000005273 aeration Methods 0.000 description 7
- 101150097746 araB gene Proteins 0.000 description 7
- 101150017736 araD gene Proteins 0.000 description 7
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 7
- 101150063552 cadB gene Proteins 0.000 description 7
- 230000002759 chromosomal effect Effects 0.000 description 7
- 238000012239 gene modification Methods 0.000 description 7
- 230000005017 genetic modification Effects 0.000 description 7
- 235000013617 genetically modified food Nutrition 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 101150052264 xylA gene Proteins 0.000 description 7
- 101150110790 xylB gene Proteins 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- 239000004952 Polyamide Substances 0.000 description 6
- 108010053763 Pyruvate Carboxylase Proteins 0.000 description 6
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 6
- OIRDTQYFTABQOQ-UHFFFAOYSA-N ara-adenosine Natural products Nc1ncnc2n(cnc12)C1OC(CO)C(O)C1O OIRDTQYFTABQOQ-UHFFFAOYSA-N 0.000 description 6
- 101150035354 araA gene Proteins 0.000 description 6
- -1 aromatic amino acid Chemical class 0.000 description 6
- 230000001851 biosynthetic effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000013604 expression vector Substances 0.000 description 6
- 229930027917 kanamycin Natural products 0.000 description 6
- 229960000318 kanamycin Drugs 0.000 description 6
- 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 6
- 229930182823 kanamycin A Natural products 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 125000003729 nucleotide group Chemical group 0.000 description 6
- 229920002647 polyamide Polymers 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 230000028327 secretion Effects 0.000 description 6
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 5
- 229920001817 Agar Polymers 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 235000019766 L-Lysine Nutrition 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 101100157012 Thermoanaerobacterium saccharolyticum (strain DSM 8691 / JW/SL-YS485) xynB gene Proteins 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 108090000637 alpha-Amylases Proteins 0.000 description 5
- 102000004139 alpha-Amylases Human genes 0.000 description 5
- 229940024171 alpha-amylase Drugs 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 210000004748 cultured cell Anatomy 0.000 description 5
- 238000006114 decarboxylation reaction Methods 0.000 description 5
- 239000012847 fine chemical Substances 0.000 description 5
- 230000004927 fusion Effects 0.000 description 5
- 108091006104 gene-regulatory proteins Proteins 0.000 description 5
- 102000034356 gene-regulatory proteins Human genes 0.000 description 5
- 238000002744 homologous recombination Methods 0.000 description 5
- 230000006801 homologous recombination Effects 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 238000002703 mutagenesis Methods 0.000 description 5
- 231100000350 mutagenesis Toxicity 0.000 description 5
- 102000039446 nucleic acids Human genes 0.000 description 5
- 108020004707 nucleic acids Proteins 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 238000005191 phase separation Methods 0.000 description 5
- 101150016257 pycA gene Proteins 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000011144 upstream manufacturing Methods 0.000 description 5
- 238000003260 vortexing Methods 0.000 description 5
- 101150011516 xlnD gene Proteins 0.000 description 5
- 230000004127 xylose metabolism Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 244000063299 Bacillus subtilis Species 0.000 description 4
- 241000186146 Brevibacterium Species 0.000 description 4
- 108010077448 Diamine N-acetyltransferase Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 108010051862 Methylmalonyl-CoA mutase Proteins 0.000 description 4
- 108010051753 Spermidine Synthase Proteins 0.000 description 4
- 102100030413 Spermidine synthase Human genes 0.000 description 4
- 102000011929 Succinate-CoA Ligases Human genes 0.000 description 4
- 108010075728 Succinate-CoA Ligases Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 230000000692 anti-sense effect Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000010353 genetic engineering Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 238000003752 polymerase chain reaction Methods 0.000 description 4
- 238000003259 recombinant expression Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 108091006106 transcriptional activators Proteins 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 230000005945 translocation Effects 0.000 description 4
- 241001515965 unidentified phage Species 0.000 description 4
- 239000011782 vitamin Substances 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- 229940088594 vitamin Drugs 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- ACIOXMJZEFKYHZ-BXKDBHETSA-N (6r,7r)-7-amino-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)N)CC=1C[N+]1=CC=CC=C1 ACIOXMJZEFKYHZ-BXKDBHETSA-N 0.000 description 3
- 108091000044 4-hydroxy-tetrahydrodipicolinate synthase Proteins 0.000 description 3
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 108020004652 Aspartate-Semialdehyde Dehydrogenase Proteins 0.000 description 3
- 101100032149 Bacillus subtilis (strain 168) pyc gene Proteins 0.000 description 3
- 241000186031 Corynebacteriaceae Species 0.000 description 3
- 108030003594 Diaminopimelate decarboxylases Proteins 0.000 description 3
- 108010014468 Dihydrodipicolinate Reductase Proteins 0.000 description 3
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102220580942 Induced myeloid leukemia cell differentiation protein Mcl-1_Y57Y_mutation Human genes 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102220517304 Phosphate-regulating neutral endopeptidase PHEX_Y107L_mutation Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 102100039895 Pyruvate carboxylase, mitochondrial Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000187747 Streptomyces Species 0.000 description 3
- 108020004530 Transaldolase Proteins 0.000 description 3
- 102100028601 Transaldolase Human genes 0.000 description 3
- 108010043652 Transketolase Proteins 0.000 description 3
- 102000014701 Transketolase Human genes 0.000 description 3
- 108700040099 Xylose isomerases Proteins 0.000 description 3
- 102100029089 Xylulose kinase Human genes 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000012190 activator Substances 0.000 description 3
- 238000013019 agitation Methods 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 101150076178 araE gene Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 101150008667 cadA gene Proteins 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000013599 cloning vector Substances 0.000 description 3
- 101150073654 dapB gene Proteins 0.000 description 3
- 101150057904 ddh gene Proteins 0.000 description 3
- 108010056578 diaminopimelate dehydrogenase Proteins 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 101150063051 hom gene Proteins 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- 150000002972 pentoses Chemical class 0.000 description 3
- DTBNBXWJWCWCIK-UHFFFAOYSA-K phosphonatoenolpyruvate Chemical compound [O-]C(=O)C(=C)OP([O-])([O-])=O DTBNBXWJWCWCIK-UHFFFAOYSA-K 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- 108091022915 xylulokinase Proteins 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 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 2
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 102000001762 6-phosphogluconolactonase Human genes 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108010014885 Arginine-tRNA ligase Proteins 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108020004638 Circular DNA Proteins 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 108700010070 Codon Usage Proteins 0.000 description 2
- 241001517047 Corynebacterium acetoacidophilum Species 0.000 description 2
- 241001485655 Corynebacterium glutamicum ATCC 13032 Species 0.000 description 2
- 241000337023 Corynebacterium thermoaminogenes Species 0.000 description 2
- 108010001625 Diaminopimelate epimerase Proteins 0.000 description 2
- 101100098219 Dictyostelium discoideum argS1 gene Proteins 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000588722 Escherichia Species 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 2
- 108010018080 L-arabinose isomerase Proteins 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
- 102000019010 Methylmalonyl-CoA Mutase Human genes 0.000 description 2
- 101100276041 Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) ctpD gene Proteins 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- 108090000472 Phosphoenolpyruvate carboxykinase (ATP) Proteins 0.000 description 2
- 102100034792 Phosphoenolpyruvate carboxykinase [GTP], mitochondrial Human genes 0.000 description 2
- 102100036134 Probable arginine-tRNA ligase, mitochondrial Human genes 0.000 description 2
- 102000009661 Repressor Proteins Human genes 0.000 description 2
- 108010034634 Repressor Proteins Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 241000187432 Streptomyces coelicolor Species 0.000 description 2
- 108010009197 Succinyldiaminopimelate transaminase Proteins 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- ZSLZBFCDCINBPY-ZSJPKINUSA-N acetyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZSLZBFCDCINBPY-ZSJPKINUSA-N 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000003282 alkyl amino group Chemical group 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
- 238000004458 analytical method Methods 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 101150024756 argS gene Proteins 0.000 description 2
- 230000037429 base substitution Effects 0.000 description 2
- 238000010923 batch production Methods 0.000 description 2
- 101150100570 bglA gene Proteins 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 229940041514 candida albicans extract Drugs 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 239000003729 cation exchange resin Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 241000186254 coryneform bacterium Species 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 108010030074 endodeoxyribonuclease MluI Proteins 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000012224 gene deletion Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 101150031558 ldc gene Proteins 0.000 description 2
- 101150041134 ldcC gene Proteins 0.000 description 2
- 101150033534 lysA gene Proteins 0.000 description 2
- 101150035025 lysC gene Proteins 0.000 description 2
- 101150076679 lysG gene Proteins 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- SJWFXCIHNDVPSH-UHFFFAOYSA-N octan-2-ol Chemical compound CCCCCCC(C)O SJWFXCIHNDVPSH-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 229930029653 phosphoenolpyruvate Natural products 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 238000006068 polycondensation reaction Methods 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000013587 production medium Substances 0.000 description 2
- 210000001236 prokaryotic cell Anatomy 0.000 description 2
- 238000002708 random mutagenesis Methods 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical compound OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 108010073086 succinyl-CoA-tetrahydrodipicolinate N-succinyltransferase Proteins 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000011573 trace mineral Substances 0.000 description 2
- 235000013619 trace mineral Nutrition 0.000 description 2
- 230000002103 transcriptional effect Effects 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000012138 yeast extract Substances 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- HAKOAZWZCJNTBF-JEDNCBNOSA-N (2s)-2,6-diaminohexanoic acid;pentane-1,5-diamine Chemical compound NCCCCCN.NCCCC[C@H](N)C(O)=O HAKOAZWZCJNTBF-JEDNCBNOSA-N 0.000 description 1
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-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
- GHOKWGTUZJEAQD-SSDOTTSWSA-N 3-[[(2s)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoic acid Chemical compound OCC(C)(C)[C@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-SSDOTTSWSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000007991 ACES buffer Substances 0.000 description 1
- 241001156739 Actinobacteria <phylum> Species 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
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- 101100326595 Arabidopsis thaliana CAD6 gene Proteins 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 102220474557 Connector enhancer of kinase suppressor of ras 1_C12S_mutation Human genes 0.000 description 1
- 241000186145 Corynebacterium ammoniagenes Species 0.000 description 1
- 241000186248 Corynebacterium callunae Species 0.000 description 1
- 241000807905 Corynebacterium glutamicum ATCC 14067 Species 0.000 description 1
- 101900105698 Corynebacterium glutamicum Homoserine dehydrogenase Proteins 0.000 description 1
- 241000133018 Corynebacterium melassecola Species 0.000 description 1
- GUBGYTABKSRVRQ-UHFFFAOYSA-N D-Cellobiose Natural products OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 102100037458 Dephospho-CoA kinase Human genes 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 101100157003 Escherichia coli (strain K12) xylF gene Proteins 0.000 description 1
- 241001522750 Escherichia coli CFT073 Species 0.000 description 1
- 101100509436 Escherichia coli iucD gene Proteins 0.000 description 1
- 102220582125 Free fatty acid receptor 2_Y90W_mutation Human genes 0.000 description 1
- 102000027487 Fructose-Bisphosphatase Human genes 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150028469 G6PDH gene Proteins 0.000 description 1
- 101150082479 GAL gene Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 102220493642 HLA class II histocompatibility antigen, DR beta 3 chain_Y55L_mutation Human genes 0.000 description 1
- 229920002488 Hemicellulose Polymers 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 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 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 101710114013 L-lysine N6-monooxygenase MbtG Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 108090000416 L-ribulose-5-phosphate 4-epimerases Proteins 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
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 101710191364 Lysine exporter LysE Proteins 0.000 description 1
- 239000007993 MOPS buffer Substances 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
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 101100463018 Mus musculus Pck1 gene Proteins 0.000 description 1
- 241000047703 Nonion Species 0.000 description 1
- 108050007429 Ornithine decarboxylase SpeF Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 108091000041 Phosphoenolpyruvate Carboxylase Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102220492709 Protein phosphatase 1 regulatory subunit 7_Y90L_mutation Human genes 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
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000209056 Secale Species 0.000 description 1
- 235000007238 Secale cereale Nutrition 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101000693619 Starmerella bombicola Lactone esterase Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 102000003673 Symporters Human genes 0.000 description 1
- 108090000088 Symporters Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 102220481557 Tapasin_Y89F_mutation Human genes 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102220573253 Tyrosine-protein kinase Fer_Y73L_mutation Human genes 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 102220591763 Voltage-gated potassium channel subunit beta-3_Y90F_mutation Human genes 0.000 description 1
- 241000319304 [Brevibacterium] flavum Species 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 108091022872 aldose 1-epimerase Proteins 0.000 description 1
- 102000020006 aldose 1-epimerase Human genes 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 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
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 101150055570 araR gene Proteins 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-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
- 238000010364 biochemical engineering Methods 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 229910000361 cobalt sulfate Inorganic materials 0.000 description 1
- 229940044175 cobalt sulfate Drugs 0.000 description 1
- KTVIXTQDYHMGHF-UHFFFAOYSA-L cobalt(2+) sulfate Chemical compound [Co+2].[O-]S([O-])(=O)=O KTVIXTQDYHMGHF-UHFFFAOYSA-L 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012136 culture method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 108010049285 dephospho-CoA kinase Proteins 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000000502 dialysis Methods 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
- 235000015872 dietary supplement Nutrition 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000011552 falling film Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 101150054547 galM gene Proteins 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 108091008053 gene clusters Proteins 0.000 description 1
- 238000003208 gene overexpression Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229910001412 inorganic anion Inorganic materials 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 230000006799 invasive growth in response to glucose limitation Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910000358 iron sulfate Inorganic materials 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 101150066555 lacZ gene Proteins 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 229940099596 manganese sulfate Drugs 0.000 description 1
- 239000011702 manganese sulphate Substances 0.000 description 1
- 235000007079 manganese sulphate Nutrition 0.000 description 1
- SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 238000001320 near-infrared absorption spectroscopy Methods 0.000 description 1
- LGQLOGILCSXPEA-UHFFFAOYSA-L nickel sulfate Chemical compound [Ni+2].[O-]S([O-])(=O)=O LGQLOGILCSXPEA-UHFFFAOYSA-L 0.000 description 1
- 229910000363 nickel(II) sulfate Inorganic materials 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 238000007500 overflow downdraw method Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 235000020030 perry Nutrition 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 101150009573 phoA gene Proteins 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 108010086966 putrescine synthase Proteins 0.000 description 1
- 229940098524 pyridoxine 1 mg Drugs 0.000 description 1
- 101150079601 recA gene Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 102220198443 rs1057520007 Human genes 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011684 sodium molybdate Substances 0.000 description 1
- 235000015393 sodium molybdate Nutrition 0.000 description 1
- TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000010902 straw Substances 0.000 description 1
- VNOYUJKHFWYWIR-ITIYDSSPSA-N succinyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCC(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 VNOYUJKHFWYWIR-ITIYDSSPSA-N 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940005863 thiamine 500 mg Drugs 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 108091008023 transcriptional regulators Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 101150059923 trc gene Proteins 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 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
- 238000000108 ultra-filtration Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 101150038987 xylR gene Proteins 0.000 description 1
- 101150033567 xylT gene Proteins 0.000 description 1
- 210000005253 yeast cell Anatomy 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
- 150000008495 β-glucosides Chemical class 0.000 description 1
Images
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
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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
- C12N9/88—Lyases (4.)
-
- 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
- C12N15/77—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora for Corynebacterium; for Brevibacterium
-
- 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.)
- C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
-
- 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
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/001—Amines; Imines
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
- C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
- C12Y101/01003—Homoserine dehydrogenase (1.1.1.3)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y114/00—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14)
- C12Y114/11—Oxidoreductases acting on paired donors, with incorporation or reduction of molecular oxygen (1.14) with 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors (1.14.11)
- C12Y114/11004—Procollagen-lysine 5-dioxygenase (1.14.11.4), i.e. lysine-hydroxylase
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y401/00—Carbon-carbon lyases (4.1)
- C12Y401/01—Carboxy-lyases (4.1.1)
- C12Y401/01018—Lysine decarboxylase (4.1.1.18)
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
リシンヒドロキシラーゼポリペプチドは、リシンN6-ヒドロキシラーゼ[EC:1.14.13.59]としても記載されているリシンヒドロキシラーゼ活性を有するポリペプチドである。リシンヒドロキシラーゼ活性を有するかの試験は、Meneely KM, and Lamb AL BIOCHEMISTRY 46 p.11930-11937 2007、及びIJ, Hsueh LC, Baldwin JEら EUROPEAN JOURNAL OF BIOCHEMISTRY 268 p.6625-6636に見出される。
(a)スペルミジン形成活性が、配列番号12に対して少なくとも80%又は少なくとも85%又は少なくとも90%又は少なくとも95%又は少なくとも98%の同一性を有するアミノ酸配列を含むスペルミジン形成ポリペプチドの活性を低下させることにより脱調節されている、あるいは
(b)プトレシン形成活性が、配列番号17に対して少なくとも80%又は少なくとも85%又は少なくとも90%又は少なくとも95%又は少なくとも98%の同一性を有するアミノ酸配列を含むプトレシン形成ポリペプチドの活性を低下させることにより脱調節されている、あるいは
(c)プトレシン形成活性が、配列番号18に対して少なくとも80%又は少なくとも85%又は少なくとも90%又は少なくとも95%又は少なくとも98%の同一性を有するアミノ酸配列を含むオルニチンデカルボキシラーゼポリペプチドの活性を低下させることにより脱調節されている、あるいは
(d)スペルミジン取り込み活性又はプトレシン取り込み活性又はスペルミジン及びプトレシン取り込み活性が、配列番号19に対して少なくとも80%又は少なくとも85%又は少なくとも90%又は少なくとも95%又は少なくとも98%の同一性を有するアミノ酸配列を含むスペルミジン取り込みポリペプチド又はプトレシン取り込みポリペプチド又はスペルミジン及びプトレシン取り込みポリペプチドの活性を低下させることにより脱調節されている、あるいは
(e)スペルミジン形成若しくは取り込み活性又はプトレシン形成若しくは取り込み活性あるいはその組み合わせが、(a)、(b)、(c)又は(d)の組み合わせの活性を低下させることにより低減されている。
LU11697の株構築
C.グルタミカムATCC 13032株を、DNA A(pInt sacB delta PEPCKとも呼ばれる)(配列番号20)で形質転換し、また「キャンベルイン」を行って、「キャンベルイン」株を得た。続いて、「キャンベルイン」株を「キャンベルアウト」して、「キャンベルアウト」株であるLU11031を得たが、これは、欠陥ホスホエノールピルビン酸カルボキシキナーゼ酵素(Delta PEPCK)をコードする改変型ホスホエノールピルビン酸カルボキシキナーゼ遺伝子(pepck)を含有する。
LU14105の株構築
LU11697株をDNA R(pInt sacB ldc bioDとも呼ばれる)(配列番号35)で形質転換し、「キャンベルイン」株を得、続いてこれを「キャンベルアウト」して、「キャンベルアウト」株であるLU14105を得た。この株は、C.グルタミカムのbioD遺伝子座に組み込まれた、その天然プロモーター(ldc)の転写制御下に大腸菌由来のリシンデカルボキシラーゼ遺伝子を含有する。
LU14635の株構築
LU14105株をDNA S(pInt sacB delta RXA02214とも呼ばれる)(配列番号36)で形質転換し、「キャンベルイン」株を得、続いてこれを「キャンベルアウト」して、「キャンベルアウト」株であるLU14635を得た。この株は、アセチルトランスフェラーゼ遺伝子の欠失を含有する。
LU14646及びLU14646デルタアセチルトランスフェラーゼの株構築
LU 14105株をDNA T(pInt sacB delta lysEとも呼ばれる)(配列番号37)で形質転換し、「キャンベルイン」株を得、続いてこれを「キャンベルアウト」して、「キャンベルアウト」株であるLU14646を得た。この株は、リシンエクスポーターlysE遺伝子の欠失を含有する。
組換え株について振盪フラスコ実験を行い、カダベリン生産を試験した。WO2005059139に記載のとおり、リシン生産と同じ培養培地及び同じ条件を用いた。対照のため、宿主株と、pClik5aMCSを含む組換え株とを並行して試験した。これらの株を、CM寒天上で、30℃で一晩前培養した。培養した細胞を、1.5mlの0.9%NaClを含むマイクロチューブに回収し、ボルテックス後、610nmでの吸光度によって細胞密度を測定した。本培養として、オートクレーブした100ml三角フラスコに入った、0.5gのCaCO3を含む10mlの生産培地に、初期OD値の1.5倍に達するまで懸濁細胞を播種した。本培養は、回転式振盪培養機(Infors AJ118, Bottmingen, Switzerland)上で、200rpmにおいて、30℃で48〜78時間行った。カダベリン及びリシンの濃度は、HPLC(Agilent 1100 Series LC system)を用いて測定した。
リシンエクスポーターをコードする遺伝子の染色体破壊のため、2回の連続的相同組換え事象によってマーカーを用いない操作を可能とする組換えプラスミドを構築した。上流用及び下流用のPCRプライマーのセット(WJK199、WJK200、WJK201及びWJK202)を用いて、野性型ATCC13032コリネバクテリウム・グルタミカム染色体DNAからlysE遺伝子の上流領域及び下流領域を含むDNA断片を増幅し、PCRプライマーと共に融合PCR用のテンプレートとして使用して、上記遺伝子の中間領域が除去されている融合断片を作製した。1039塩基対のサイズの融合PCR産物を精製し、SpeIとXbaIで消化して、同じ制限酵素で消化したpInt sacBベクター(C.グルタミカムのゲノム遺伝子座において配列を統合する(Beckerら(2005), Applied and Environmental Microbiology, 71 (12), 8587-8596頁))中に挿入した。
WJK199
5’-TCTCACTAGTGCAGCAAGGATAATGTGTGC-3’
WJK200
5’-GTTGTCTAGAGCTGCCAACAATGGTCTTGG-3’
WJK201
5’-CACGACGACGTTGATCCAGCGGTCCGATGGACAGTAAAAG-3’
WJK 202
5’-CTTTTACTGTCCATCGGACCGCTGGATCAACGTCGTCGTG-3’
振盪フラスコ培養でのカダベリン生産
上述した菌株の振盪フラスコ培養でのカダベリン生産:
LU1105株、LU14635株、LU14646株、及びLU14646デルタアセチルトランスフェラーゼ株をカダベリン生産について分析した。lysE遺伝子及びアセチルトランスフェラーゼ遺伝子の欠失を有する上記組換え株について振盪フラスコ実験を行い、カダベリン生産を試験した。WO2005059139に記載のとおり、リシン生産と同じ培養培地及び同じ条件を用いた。対照のため、宿主株と、欠失/破壊lysE遺伝子を有する組換え株とを並行して試験した。これらの株を、CM寒天上で、30℃で一晩前培養した。培養した細胞を、1.5mlの0.9%NaClを含むマイクロチューブに回収し、ボルテックス後、610nmでの吸光度によって細胞密度を測定した。本培養として、オートクレーブした100ml三角フラスコに入った、0.5gのCaCO3を含む10mlの生産培地に、初期OD値の1.5倍に達するまで懸濁細胞を播種した。本培養は、回転式振盪培養機(Infors AJ118, Bottmingen, Switzerland)上で、200rpmにおいて、30℃で48〜78時間行った。カダベリン及びリシンの濃度は、HPLC(Agilent 1100 Series LC system)を用いて測定した。
リシンデカルボキシラーゼ分泌生物の株構築
機能性リシンデカルボキシラーゼを分泌可能な株を構築するために、上述したPSODプロモーター、ストレプトマイセス・コエリコロル(Streptomyces coelicolor)由来のアルファアミラーゼのシグナル配列、及びLDC遺伝子を、PCRプライマー伸長により融合し、クローニングして、ベクターpCLIK5A PSOD ldc sigseqアルファアミラーゼ(配列番号41)を得た。得られたベクターをLU14635株に形質転換する。上述したように振盪フラスコにおいて増殖及びインキュベーションした後、培養上清中のリシンの量が、移行/分泌シグナル配列を有しないldCを発現する対照と比較して低減していることが見出される。
DAPの生産のためのC5糖の利用のための株構築
キシロースの利用に関する大腸菌遺伝子(キシロースイソメラーゼ及びキシルロースキナーゼxylAB)をPCR融合法によりC.グルタミカム由来のPgroプロモーターに融合し、PCRにより増幅し、ベクターpGの制限部位XhoI及びMluIに挿入して、ベクターpG Pgro xylAB(配列番号39)を得た。プラスミドをLU14635株に形質転換すると共に、キシロース利用遺伝子を含まない空の対照プラスミドpGを形質転換して、LU14635 pG株及びLU14635 pG Pgro xylAB株を得た。
振盪フラスコ実験を以下のように実施した:
上述した株の振盪フラスコ培養でのカダベリン生産。LU14635 pG株及びpG Pgro Xyl AB株をカダベリン生産について分析した。キシロースオペロン遺伝子を過剰発現するためにプラスミドによる組換え株について振盪フラスコ実験を行い、カダベリン生産を試験した。これらの株を、25μg/mlカナマイシンを含むCM寒天上で、30℃で一晩前培養した。培養した細胞を、1.5mlの0.9%NaClを含むマイクロチューブに回収し、ボルテックス後、610nmでの吸光度によって細胞密度を測定した。本培養として、オートクレーブした100ml三角フラスコに入った、25μg/mlの濃度のカナマイシンを添加した10mlのMDAP培地に、初期OD値の1.5倍に達するまで懸濁細胞を播種した。本培養は、回転式振盪培養機(Infors AJ118, Bottmingen, Switzerland)上で、200rpmにおいて、30℃で48〜78時間行った。カダベリン及びリシン並びに残留糖の濃度は、HPLC(Agilent 1100 Series LC system)を用いて測定した。
MDAP培地は以下の成分から構成される:
硫酸アンモニウム 25g/L
酵母エキス Difco 15g/L
ビタミンストック 15ml/L
塩溶液MDAP 100ml/L
微量元素溶液: 15ml/L
ピリドキシン 1mg/ml 1ml/L
糖(グルコース又はキシロース) 60〜50g/L
ACES 78g/L
MOPS 21g/L
CaCO3 15g/L
ビオチン 300mg/l
チアミン 500mg/l
ニコチンアミド 600mg/l
パントテン酸 2000mg/l
ビタミン溶液の添加 15ml/l
クエン酸 2g/L
硫酸カルシウム 1.5g/L
リン酸カリウム 25g/L
硫酸マグネシウム 12.5g/L
硫酸鉄(II) 700mg/L
硫酸亜鉛 300mg/L
硫酸マンガン 150mg/L
クエン酸 2.1g/L
ホウ酸 300mg/L
硫酸コバルト 240mg/L
硫酸銅 300mg/L
硫酸ニッケル 200mg/L
モリブデン酸ナトリウム 50mg/L
バチルス・ズブチリス由来のキシロース利用遺伝子を用いたDAPの生産のためのC5糖(ペントース)の利用のための株構築
キシロースの利用についてのバチルス・ズブチリス遺伝子(すなわちキシロースイソメラーゼ及びキシルロースキナーゼ)を、PCR反応によりC.グルタミカム由来のPSODプロモーターと融合し、PCRにより増幅し、ベクターpGの制限部位XhoI及びMluIに挿入して、ベクターpG PSOD xyl AB B.ズブチリスを得た。このベクターの配列は配列番号40である。このプラスミドをLU14635株に形質転換し、並びにキシロース利用遺伝子を含まない空の対照プラスミドpGを形質転換して、LU14635 pG株及びLU14635 pG Pgro xylAB B.ズブチリス株を得た。
振盪フラスコ実験を以下のように実施した:
上述した菌株の振盪フラスコ培養でのカダベリン生産。LU14635 pG株及びpG Pgro xylAB B.ズブチリス株をカダベリン生産について分析した。キシロースオペロン遺伝子を過剰発現するプラスミドによる組換え株について振盪フラスコ実験を行い、カダベリン生産を試験した。これらの株を、25μg/mlカナマイシンを含むCM寒天上で、30℃で一晩前培養した。培養した細胞を、1.5mlの0.9%NaClを含むマイクロチューブに回収し、ボルテックス後、610nmでの吸光度によって細胞密度を測定した。本培養として、オートクレーブした100ml三角フラスコに入った、25μg/mlの濃度のカナマイシンを添加した10mlのMDAP培地に、初期OD値の1.5倍に達するまで懸濁細胞を播種した。本培養は、回転式振盪培養機(Infors AJ118, Bottmingen, Switzerland)上で、200rpmにおいて、30℃で48〜78時間行った。カダベリン及びリシン並びに残留糖の濃度は、HPLC(Agilent 1100 Series LC system)を用いて測定した。
リシンデカルボキシラーゼの分泌のための株構築。脱炭酸についての大腸菌ldc遺伝子を、PCR融合によりC.グルタミカム由来のPSODプロモーター、及びストレプトマイセス・コエリコロル(Streptomyces coelicolor)のアルファアミラーゼのシグナル配列と融合する。この融合した遺伝子を、次にpCLIKベクターにクローニングして、pCLIK PSOD ldc alpha-amylase sigseq(配列番号41)を得る。このプラスミドを形質転換してLU14635 pCLIK PSOD ldc alpha amy sigseq株を得る。上述した株の振盪フラスコ培養でのカダベリン生産を行う。LU14635 pCLIK株及びpCLIK PSOD ldc alpha amy sigseq株をカダベリン生産について分析する。振盪フラスコ実験を、C.グルタミカムにより分泌されるldcを過剰発現するプラスミドによる組換え株で実施して、カダベリン生産を試験する。これらの株を、25μg/mlカナマイシンを含むCM寒天上で、30℃で一晩前培養する。培養した細胞を、1.5mlの0.9%NaClを含むマイクロチューブに回収し、ボルテックス後、610nmでの吸光度によって細胞密度を測定する。本培養として、オートクレーブした100ml三角フラスコに入った、25μg/mlの濃度のカナマイシンを添加した10mlのMDAP培地に、初期OD値の1.5倍に達するまで懸濁細胞を播種する。本培養は、回転式振盪培養機(Infors AJ118, Bottmingen, Switzerland)上で、200rpmにおいて、30℃で48〜78時間行う。カダベリン及びリシン並びに残留糖の濃度は、HPLC(Agilent 1100 Series LC system)を用いて測定する。LU14635 pCLIK PSOD ldc alpha amy sigseq株は、細胞上清中にリシンを生産しないのに対し、LU14635 pCLIK株はそうではなく、またLU14635 pCLIK PSOD ldc alpha amy sigseq株はLU14635 pCLIK株よりも多くのカダベリンを生産することがわかる。
Claims (22)
- (a)配列番号1と少なくとも90%の同一性を有するアミノ酸配列を含み、かつリシンデカルボキシラーゼ活性を有するポリペプチドの発現による、細胞内リシンデカルボキシラーゼ活性及び
(b)配列番号3と少なくとも95%の同一性を有するアミノ酸配列を含み、かつリシンエクスポーター活性を有するポリペプチドの欠失又は破壊による、増強されたリシンインポート活性
を含み、かつ
(c)配列番号11と少なくとも95%の同一性を有するアミノ酸配列を含み、かつアセチルカダベリン形成活性を有するポリペプチドの欠失又は破壊により、アセチルカダベリン形成活性がない
微生物であって、コリネバクテリウム・グルタミカム(Corynebacterium glutamicum)である、微生物。 - 高いリシン生産能を有する、請求項1に記載の微生物。
- アミノプロピルカダベリン形成活性がない又は低減されている、請求項1又は2に記載の微生物。
- アミノプロピルカダベリン形成活性が、配列番号12と少なくとも90%の同一性を有するアミノ酸配列を含み、かつアミノプロピルカダベリン形成活性を有するポリペプチドの活性を低下させることにより低減される、請求項1〜3のいずれか1項に記載の微生物。
- ホモセリンデヒドロゲナーゼ活性がない又は低減されている、請求項1〜4のいずれか1項に記載の微生物。
- ホモセリンデヒドロゲナーゼ活性が、配列番号13、14又は15と少なくとも90%の同一性を有するアミノ酸配列を含み、かつホモセリンデヒドロゲナーゼ活性を有するポリペプチドの活性を低下させることにより低減される、請求項1〜5のいずれか1項に記載の微生物。
- リシン分解活性がない又は低減されている、請求項1〜6のいずれか1項に記載の微生物。
- リシン分解活性が、配列番号16と少なくとも90%の同一性を有するアミノ酸配列を含み、かつリシンヒドロキシラーゼ活性を有する少なくとも1つのポリペプチドの活性を低下させることにより低減される、請求項1〜7のいずれか1項に記載の微生物。
- 請求項1〜8のいずれか1項に記載の微生物、及び該微生物の増殖に適した培養培地を含むカダベリン生産系。
- 培養培地がリシンを含む、請求項9に記載のカダベリン生産系。
- 請求項1〜8のいずれか1項に記載の微生物を発酵することを含む、カダベリンの生産方法。
- 培養培地がリシンを含む、請求項11に記載の方法。
- 培養培地中のカダベリンの濃度(mol/l)が、
(a)アセチルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い、又は
(b)アミノプロピルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い、
請求項11又は12に記載の方法。 - 培養培地中のカダベリンの濃度(mol/l)が、アセチルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い、請求項11〜13のいずれか1項に記載の方法。
- 請求項11〜14のいずれか1項に記載の方法を使用して、カダベリンの濃度(mol/l)が、
(a)アセチルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い、又は
(b)アミノプロピルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い
培養培地を製造する方法。 - カダベリンの濃度(mol/l)がアセチルカダベリンの濃度(mol/l)よりも少なくとも1.2倍高い培養培地を製造する方法である、請求項15に記載の方法。
- 請求項11〜14のいずれか1項に記載の方法を使用して、少なくとも0.25mol/lのカダベリンを含むが、
(a)0.1mol/l以下のアセチルカダベリン、又は
(b)0.1mol/l以下のアミノプロピルカダベリン
を含む培養培地を製造する方法。 - 請求項11〜14のいずれか1項に記載の方法を使用して、少なくとも0.25mol/lのカダベリンを含むが0.1mol/l以下のアセチルカダベリンを含む培養培地を製造する方法。
- カダベリンの生産のための、請求項1〜8のいずれか1項に記載の微生物又は請求項9〜10のいずれか1項に記載のカダベリン生産系の使用。
- 請求項11〜14のいずれか1項に記載の方法における、請求項1〜8のいずれか1項に記載の微生物又は請求項9〜10のいずれか1項に記載のカダベリン生産系の使用。
- 請求項15〜18のいずれか1項に記載の方法によって培養培地を製造し、培養培地からカダベリンを回収することを含む、カダベリンの回収方法。
- 請求項11〜14のいずれか1項に記載の方法を使用して培養培地を製造し、培養培地からカダベリンを精製することを含む、カダベリンの精製方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US28722709P | 2009-12-17 | 2009-12-17 | |
US61/287,227 | 2009-12-17 | ||
EP09179642 | 2009-12-17 | ||
EP09179642.5 | 2009-12-17 | ||
PCT/EP2010/069802 WO2011073278A1 (en) | 2009-12-17 | 2010-12-15 | Processes and recombinant microorganisms for the production of cadaverine |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2013514069A JP2013514069A (ja) | 2013-04-25 |
JP5960604B2 true JP5960604B2 (ja) | 2016-08-02 |
Family
ID=44246824
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012543730A Expired - Fee Related JP5960604B2 (ja) | 2009-12-17 | 2010-12-15 | カダベリンの生産のための方法及び組換え微生物 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20120295317A1 (ja) |
EP (1) | EP2513302A1 (ja) |
JP (1) | JP5960604B2 (ja) |
KR (1) | KR20120094137A (ja) |
CN (2) | CN102753682A (ja) |
DE (1) | DE112010004851T5 (ja) |
WO (1) | WO2011073278A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022244809A1 (ja) | 2021-05-19 | 2022-11-24 | 旭化成株式会社 | ジアミン生産能を有する組換え微生物およびジアミンの製造方法 |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2790919C (en) * | 2010-02-23 | 2019-02-26 | Toray Industries, Inc. | Process for production of cadaverine |
KR101231897B1 (ko) * | 2010-08-03 | 2013-02-08 | 한국과학기술원 | 카다베린 고생성능을 가지는 변이 미생물 및 이를 이용한 카다베린의 제조방법 |
WO2012114256A1 (en) | 2011-02-22 | 2012-08-30 | Basf Se | Processes and recombinant microorganisms for the production of cadaverine |
CN102424811A (zh) * | 2011-12-13 | 2012-04-25 | 天津科技大学 | 一种产尸胺工程菌 |
WO2013093737A1 (en) * | 2011-12-22 | 2013-06-27 | Basf Se | Processes and recombinant microorganisms for the production of fine chemicals |
TWI510621B (zh) * | 2013-07-08 | 2015-12-01 | Cj Cheiljedang Corp | 具有增加之腐胺生產力之重組微生物及使用該微生物之製造腐胺之方法 |
JP6337899B2 (ja) | 2013-08-23 | 2018-06-06 | 味の素株式会社 | 1,5−ペンタジアミンの製造方法 |
BR112016029386A2 (pt) * | 2014-06-16 | 2017-10-17 | Invista Tech Sarl | métodos, reagentes e células para biossintetizar compostos |
US10647976B2 (en) | 2014-06-26 | 2020-05-12 | Cathay Biotech Inc. | Expression of polypeptides involved in lysine decarboxylation, and methods and applications thereof |
WO2016169810A1 (de) | 2015-04-20 | 2016-10-27 | Basf Se | Zweikomponentige beschichtungsmassen |
CN105368766B (zh) * | 2015-05-20 | 2019-07-05 | 天津科技大学 | 一株生产戊二胺的基因工程菌及其制备戊二胺的方法 |
CN105441496A (zh) * | 2015-12-22 | 2016-03-30 | 天津科技大学 | 一种提高微生物利用糖类发酵生产尸胺的方法 |
CN110291192B (zh) * | 2016-12-30 | 2023-12-08 | 上海凯赛生物技术股份有限公司 | 在可滴定氨基酸具有修饰的赖氨酸脱羧酶 |
EP3562837A4 (en) * | 2016-12-30 | 2020-12-30 | Cathay Biotech Inc. | MODIFIED LYSIN DECARBOXYLASE ENZYMES |
US11155840B2 (en) | 2017-07-06 | 2021-10-26 | Cathay Biotech Inc. | Heterologous expression of thermophilic lysine decarboxylase and uses thereof |
EP3428282A1 (en) * | 2017-07-11 | 2019-01-16 | Alderys | Ectoine-producing yeast |
CN111315866B (zh) * | 2017-09-22 | 2023-09-22 | 上海凯赛生物技术股份有限公司 | 碳水化合物结合模块的异源表达及其用于尸胺生产的用途 |
EP3887517A1 (en) * | 2018-11-30 | 2021-10-06 | Zymergen Inc. | Engineered biosynthetic pathways for production of 1,5-diaminopentane by fermentation |
CN111118077B (zh) * | 2020-01-09 | 2022-03-29 | 南京工业大学 | 一种利用玉米芯水解液中木糖一步发酵生产1,5-戊二胺的方法 |
CN115490761B (zh) * | 2021-11-01 | 2023-06-09 | 中国科学院天津工业生物技术研究所 | 基于赖氨酸外排蛋白构建的重组微生物及生产赖氨酸的方法 |
CN115109805A (zh) * | 2022-03-29 | 2022-09-27 | 东华大学 | 一种微生物制备5-氨基-1-戊醇的方法 |
Family Cites Families (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1048222B (de) | 1956-01-10 | 1958-12-31 | Hoechst Ag | Foerderband aus Kunststoff |
DE19548222A1 (de) | 1995-12-22 | 1997-06-26 | Forschungszentrum Juelich Gmbh | Verfahren zur mikrobiellen Herstellung von Aminosäuren durch gesteigerte Aktivität von Exportcarriern |
US6893848B1 (en) | 1999-04-19 | 2005-05-17 | Kyowa Hakko Kogyo Co., Ltd. | Desensitized aspartokinase |
US20020086371A1 (en) | 1999-07-07 | 2002-07-04 | Degussa-Huls Aktiengesellschaft | L-lysine-producing corynebacteria and process for the preparation of L-lysine |
JP4623825B2 (ja) | 1999-12-16 | 2011-02-02 | 協和発酵バイオ株式会社 | 新規ポリヌクレオチド |
US20030175911A1 (en) | 2000-03-20 | 2003-09-18 | Stephen Hans | Process for the preparation of L-amino acids with amplification of the zwf gene |
JP5553394B2 (ja) | 2001-02-01 | 2014-07-16 | 東レ株式会社 | カダベリンの製造方法 |
EP1577369B1 (en) | 2002-12-26 | 2013-11-20 | Idemitsu Kosan Co., Ltd. | Method for removing sulfur compound in hydrocarbon-containing gas |
JP2004222569A (ja) * | 2003-01-22 | 2004-08-12 | Toray Ind Inc | コリネ型細菌、ならびにカダベリンもしくはその塩およびそれらの製造方法 |
JP2004261150A (ja) * | 2003-03-04 | 2004-09-24 | Ajinomoto Co Inc | 目的物質の製造法 |
JP4254306B2 (ja) * | 2003-03-31 | 2009-04-15 | 東レ株式会社 | カダベリンの製造方法 |
DE10359660A1 (de) | 2003-12-18 | 2005-07-28 | Basf Ag | Psod-Expressionseinheiten |
DE10359594A1 (de) | 2003-12-18 | 2005-07-28 | Basf Ag | PEF-TU-Expressionseinheiten |
US20080032374A1 (en) | 2003-12-18 | 2008-02-07 | Basf Aktiengesellschaft | Method for the Preparation of Lysine by Fermentation of Corynebacterium Glutamicum |
DE10359661A1 (de) | 2003-12-18 | 2005-07-28 | Basf Ag | Genvarianten die für Proteine aus dem Stoffwechselweg von Feinchemikalien codieren |
RU2316588C1 (ru) | 2004-01-30 | 2008-02-10 | Адзиномото Ко., Инк. | Бактерия - продуцент l-аминокислоты и способ получения l-аминокислоты (варианты) |
US8003367B2 (en) | 2004-03-16 | 2011-08-23 | Ajinomoto Co., Inc. | Method for producing L-amino acids by fermentation using bacteria having enhanced expression of xylose utilization genes |
DE102004061846A1 (de) | 2004-12-22 | 2006-07-13 | Basf Ag | Mehrfachpromotoren |
JP2009501550A (ja) | 2005-07-18 | 2009-01-22 | ビーエーエスエフ ソシエタス・ヨーロピア | メチオニン生産組換え微生物 |
BRPI0612900A8 (pt) | 2005-07-18 | 2022-07-19 | Basf Ag | Métodos para produzir metionina, para aperfeiçoar o uso de dmds para produção de metionina, e, para identificar um alelo mutante, composição, produto contendo metionina, microorganismo, gene isolado, o-acetil-homosserina sulfidrilase mutante ou enzimas de o-succinil-homosserina sulfidrilase, e organismo |
BRPI0614891A2 (pt) | 2005-08-18 | 2012-12-25 | Basf Se | mÉtodo, dispositivo e elemento de programa para determinar um organismo com eficiÊncia aumentada para a sÍntese de metionina, meio legÍvel por computador, mÉtodo para produzir um organismo, organismo, mÉtodos para produzir um microorganismo do gÊnero corynebacterium e do gÊnero escherichia com eficiÊncia aumentada da produÇço de metionina, microorganismos dos gÊneros corynebacterium e escherichia, uso de qualquer um dos organismos, e, mÉtodo para produzir metionina |
CN101389765B (zh) * | 2006-03-30 | 2012-08-22 | 巴斯夫欧洲公司 | 生产尸胺的方法 |
US20090325244A1 (en) | 2006-10-24 | 2009-12-31 | Basf Se | Method of increasing gene expression using modified codon usage |
DE102007005072A1 (de) | 2007-02-01 | 2008-08-07 | Evonik Degussa Gmbh | Verfahren zur fermentativen Herstellung von Cadaverin |
BRPI0903495B1 (pt) * | 2008-04-10 | 2019-01-29 | Korea Advanced Inst Sci & Tech | microorganismos mutantes com capacidade de produzir putrescina e método para produção de putrescina utilizando os mesmos |
-
2010
- 2010-12-15 CN CN2010800638898A patent/CN102753682A/zh active Pending
- 2010-12-15 JP JP2012543730A patent/JP5960604B2/ja not_active Expired - Fee Related
- 2010-12-15 EP EP10795316A patent/EP2513302A1/en not_active Withdrawn
- 2010-12-15 WO PCT/EP2010/069802 patent/WO2011073278A1/en active Application Filing
- 2010-12-15 KR KR1020127018563A patent/KR20120094137A/ko not_active Application Discontinuation
- 2010-12-15 CN CN201611070521.XA patent/CN106906175A/zh active Pending
- 2010-12-15 DE DE112010004851T patent/DE112010004851T5/de not_active Withdrawn
- 2010-12-15 US US13/516,034 patent/US20120295317A1/en not_active Abandoned
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022244809A1 (ja) | 2021-05-19 | 2022-11-24 | 旭化成株式会社 | ジアミン生産能を有する組換え微生物およびジアミンの製造方法 |
Also Published As
Publication number | Publication date |
---|---|
DE112010004851T5 (de) | 2012-09-20 |
CN106906175A (zh) | 2017-06-30 |
EP2513302A1 (en) | 2012-10-24 |
KR20120094137A (ko) | 2012-08-23 |
CN102753682A (zh) | 2012-10-24 |
WO2011073278A1 (en) | 2011-06-23 |
JP2013514069A (ja) | 2013-04-25 |
US20120295317A1 (en) | 2012-11-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5960604B2 (ja) | カダベリンの生産のための方法及び組換え微生物 | |
JP6067588B2 (ja) | カダベリンの生産のための方法及び組換え微生物 | |
JP5210295B2 (ja) | カダベリンの生産方法 | |
US9644220B2 (en) | Processes and recombinant microorganisms for the production of fine chemicals | |
CN103146593B (zh) | 生产l-氨基酸的微生物和生产l-氨基酸的方法 | |
US20150140614A1 (en) | Variants of the promoter of the gap gene coding for glyceraldehyde-3-phosphate dehydrogenase | |
WO2017100376A9 (en) | Promoters from corynebacterium glutamicum | |
US20090029425A1 (en) | Process for the production of beta-lysine | |
EP2841568B1 (en) | Feedback-resistant alpha-isopropylmalate synthases | |
WO2004113550A1 (ja) | L−グルタミン酸の製造法 | |
CN116583605A (zh) | L-氨基酸的制造方法 | |
MXPA00010779A (es) | Proceso para la produccion por fermentacion de l-lisina empleando bacterias corineformes. | |
JPWO2013154182A1 (ja) | アミノ酸の製造法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20131210 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150210 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150430 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150609 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151020 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160219 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160314 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20160524 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160623 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5960604 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |