CA2533838A1 - Improved ketoreductase polypeptides and related polynucleotides - Google Patents
Improved ketoreductase polypeptides and related polynucleotides Download PDFInfo
- Publication number
- CA2533838A1 CA2533838A1 CA002533838A CA2533838A CA2533838A1 CA 2533838 A1 CA2533838 A1 CA 2533838A1 CA 002533838 A CA002533838 A CA 002533838A CA 2533838 A CA2533838 A CA 2533838A CA 2533838 A1 CA2533838 A1 CA 2533838A1
- Authority
- CA
- Canada
- Prior art keywords
- seq
- kred
- polypeptide
- activity
- polynucleotide
- 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.)
- Abandoned
Links
- 101001110310 Lentilactobacillus kefiri NADP-dependent (R)-specific alcohol dehydrogenase Proteins 0.000 title claims abstract description 257
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 216
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 213
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 213
- 102000040430 polynucleotide Human genes 0.000 title claims abstract description 96
- 108091033319 polynucleotide Proteins 0.000 title claims abstract description 96
- 239000002157 polynucleotide Substances 0.000 title claims abstract description 96
- 230000000694 effects Effects 0.000 claims abstract description 106
- 230000014509 gene expression Effects 0.000 claims abstract description 44
- 239000013598 vector Substances 0.000 claims abstract description 34
- 239000002773 nucleotide Substances 0.000 claims abstract description 17
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 17
- 101000611441 Solanum lycopersicum Pathogenesis-related leaf protein 6 Proteins 0.000 claims description 97
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 58
- 150000007523 nucleic acids Chemical group 0.000 claims description 46
- 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 42
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 37
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 28
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 24
- 238000006467 substitution reaction Methods 0.000 claims description 19
- 125000000539 amino acid group Chemical group 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 230000001105 regulatory effect Effects 0.000 claims description 11
- 102200082872 rs34866629 Human genes 0.000 claims description 10
- 238000012217 deletion Methods 0.000 claims description 8
- 230000037430 deletion Effects 0.000 claims description 8
- 238000003780 insertion Methods 0.000 claims description 8
- 230000037431 insertion Effects 0.000 claims description 8
- 102200075063 rs104894696 Human genes 0.000 claims description 7
- 102220283746 rs1555924522 Human genes 0.000 claims description 7
- 102200001739 rs72552725 Human genes 0.000 claims description 7
- 239000012634 fragment Substances 0.000 claims description 6
- 101100462457 African swine fever virus (strain Badajoz 1971 Vero-adapted) Ba71V-049 gene Proteins 0.000 claims description 5
- 102220624447 Iron-sulfur cluster assembly enzyme ISCU, mitochondrial_N90D_mutation Human genes 0.000 claims description 5
- 238000011534 incubation Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 102200017268 rs121918392 Human genes 0.000 claims description 5
- 102200063469 rs869312823 Human genes 0.000 claims description 5
- 230000000295 complement effect Effects 0.000 claims description 4
- 229910052720 vanadium Inorganic materials 0.000 claims description 4
- 102220584188 Cellular tumor antigen p53_A86V_mutation Human genes 0.000 claims description 3
- 102220591051 Cellular tumor antigen p53_T18A_mutation Human genes 0.000 claims description 3
- 102220480531 GSK3B-interacting protein_K85R_mutation Human genes 0.000 claims description 3
- 102220468645 HLA class II histocompatibility antigen, DP beta 1 chain_K98R_mutation Human genes 0.000 claims description 3
- 102220474111 Inorganic pyrophosphatase 2, mitochondrial_S66G_mutation Human genes 0.000 claims description 3
- 102220599171 Leukocyte cell-derived chemotaxin-2_H67L_mutation Human genes 0.000 claims description 3
- 102220523817 Sortilin-related receptor_A48T_mutation Human genes 0.000 claims description 3
- 102220470569 Tryptase delta_K79R_mutation Human genes 0.000 claims description 3
- 102220226091 rs1064794928 Human genes 0.000 claims description 3
- 102220028864 rs145479679 Human genes 0.000 claims description 3
- 102220278884 rs1554569658 Human genes 0.000 claims description 3
- 102220283130 rs1555750818 Human genes 0.000 claims description 3
- 102220075807 rs202025584 Human genes 0.000 claims description 3
- 102200118232 rs33959340 Human genes 0.000 claims description 3
- 102220071199 rs376603102 Human genes 0.000 claims description 3
- 102220037054 rs587780188 Human genes 0.000 claims description 3
- 102220213921 rs762028131 Human genes 0.000 claims description 3
- 102220082365 rs863224257 Human genes 0.000 claims description 3
- 102220103310 rs878854070 Human genes 0.000 claims description 3
- 102220160611 rs886048391 Human genes 0.000 claims description 3
- 239000004295 calcium sulphite Substances 0.000 claims 2
- 102220353591 c.16A>G Human genes 0.000 claims 1
- 102200006815 rs11546660 Human genes 0.000 claims 1
- 102200098368 rs137852607 Human genes 0.000 claims 1
- 102220274086 rs1379627026 Human genes 0.000 claims 1
- 102220306787 rs1557084218 Human genes 0.000 claims 1
- 102200088301 rs2287555 Human genes 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 108020004705 Codon Proteins 0.000 abstract description 21
- 230000009467 reduction Effects 0.000 abstract description 17
- 150000002576 ketones Chemical class 0.000 abstract description 15
- 230000000707 stereoselective effect Effects 0.000 abstract description 3
- 102220242548 rs750080180 Human genes 0.000 description 177
- 102220609844 AP-1 complex subunit sigma-1A_P14A_mutation Human genes 0.000 description 94
- 210000004027 cell Anatomy 0.000 description 90
- 108090000623 proteins and genes Proteins 0.000 description 48
- 238000000034 method Methods 0.000 description 47
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) 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-NNYOXOHSSA-O 0.000 description 42
- 102200128132 rs10896380 Human genes 0.000 description 37
- 108091026890 Coding region Proteins 0.000 description 29
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 28
- 239000013604 expression vector Substances 0.000 description 28
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 27
- 102000004190 Enzymes Human genes 0.000 description 24
- 108090000790 Enzymes Proteins 0.000 description 24
- 229940088598 enzyme Drugs 0.000 description 24
- 235000001014 amino acid Nutrition 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 20
- 102220055147 rs727504148 Human genes 0.000 description 20
- 108010076504 Protein Sorting Signals Proteins 0.000 description 18
- 102000039446 nucleic acids Human genes 0.000 description 18
- 108020004707 nucleic acids Proteins 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 17
- 230000010076 replication Effects 0.000 description 17
- 238000010438 heat treatment Methods 0.000 description 16
- 239000013612 plasmid Substances 0.000 description 16
- 239000006166 lysate Substances 0.000 description 15
- 230000035772 mutation Effects 0.000 description 14
- 241000588724 Escherichia coli Species 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 13
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 13
- 238000012216 screening Methods 0.000 description 13
- 108020004414 DNA Proteins 0.000 description 12
- 108010050375 Glucose 1-Dehydrogenase Proteins 0.000 description 12
- 230000008929 regeneration Effects 0.000 description 12
- 238000011069 regeneration method Methods 0.000 description 12
- 230000007423 decrease Effects 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 235000018102 proteins Nutrition 0.000 description 11
- 102000004169 proteins and genes Human genes 0.000 description 11
- 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 10
- 238000002835 absorbance Methods 0.000 description 10
- 229960005091 chloramphenicol Drugs 0.000 description 10
- 239000008103 glucose Substances 0.000 description 10
- 239000000758 substrate Substances 0.000 description 10
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 8
- 240000006439 Aspergillus oryzae Species 0.000 description 8
- 102220355011 c.440T>C Human genes 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 102200082890 rs33972047 Human genes 0.000 description 8
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 7
- -1 (R)-4-cyano-3-hydroxybutyric acid ester Chemical class 0.000 description 7
- 241000222292 [Candida] magnoliae Species 0.000 description 7
- 230000002538 fungal effect Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 239000004382 Amylase Substances 0.000 description 6
- 108010065511 Amylases Proteins 0.000 description 6
- 102000013142 Amylases Human genes 0.000 description 6
- 101000755953 Bacillus subtilis (strain 168) Ribosome maturation factor RimP Proteins 0.000 description 6
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 125000003412 L-alanyl group Chemical group [H]N([H])[C@@](C([H])([H])[H])(C(=O)[*])[H] 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 235000019418 amylase Nutrition 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000013592 cell lysate Substances 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 230000008488 polyadenylation Effects 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- 102200072983 rs1630312 Human genes 0.000 description 6
- 102220277134 rs776745497 Human genes 0.000 description 6
- 102200014842 rs78136490 Human genes 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 241000351920 Aspergillus nidulans Species 0.000 description 5
- 241000228245 Aspergillus niger Species 0.000 description 5
- 101000757144 Aspergillus niger Glucoamylase Proteins 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 241000218377 Magnoliaceae Species 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 5
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 5
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 230000002255 enzymatic effect Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000010354 integration Effects 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229950006238 nadide Drugs 0.000 description 5
- 235000004400 serine Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 244000063299 Bacillus subtilis Species 0.000 description 4
- 235000014469 Bacillus subtilis Nutrition 0.000 description 4
- 241001302584 Escherichia coli str. K-12 substr. W3110 Species 0.000 description 4
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 4
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 4
- 108010048241 acetamidase Proteins 0.000 description 4
- 108090000637 alpha-Amylases Proteins 0.000 description 4
- 102000004139 alpha-Amylases Human genes 0.000 description 4
- 229940024171 alpha-amylase Drugs 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000007853 buffer solution Substances 0.000 description 4
- OHLRLMWUFVDREV-UHFFFAOYSA-N ethyl 4-chloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CCl OHLRLMWUFVDREV-UHFFFAOYSA-N 0.000 description 4
- 101150109249 lacI gene Proteins 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 238000010369 molecular cloning Methods 0.000 description 4
- 238000002703 mutagenesis Methods 0.000 description 4
- 231100000350 mutagenesis Toxicity 0.000 description 4
- 102200046175 rs104894187 Human genes 0.000 description 4
- 102220124941 rs34574788 Human genes 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical class CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 3
- 102000007698 Alcohol dehydrogenase Human genes 0.000 description 3
- 108010021809 Alcohol dehydrogenase Proteins 0.000 description 3
- 102100034044 All-trans-retinol dehydrogenase [NAD(+)] ADH1B Human genes 0.000 description 3
- 101710193111 All-trans-retinol dehydrogenase [NAD(+)] ADH4 Proteins 0.000 description 3
- 108010037870 Anthranilate Synthase Proteins 0.000 description 3
- 102000004580 Aspartic Acid Proteases Human genes 0.000 description 3
- 108010017640 Aspartic Acid Proteases Proteins 0.000 description 3
- 241000193830 Bacillus <bacterium> Species 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000223221 Fusarium oxysporum Species 0.000 description 3
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 102100027612 Kallikrein-11 Human genes 0.000 description 3
- 125000000570 L-alpha-aspartyl group Chemical group [H]OC(=O)C([H])([H])[C@]([H])(N([H])[H])C(*)=O 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 241000235403 Rhizomucor miehei Species 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- 101710152431 Trypsin-like protease Proteins 0.000 description 3
- IXKSXJFAGXLQOQ-XISFHERQSA-N WHWLQLKPGQPMY Chemical compound C([C@@H](C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)NC(=O)[C@@H](N)CC=1C2=CC=CC=C2NC=1)C1=CNC=N1 IXKSXJFAGXLQOQ-XISFHERQSA-N 0.000 description 3
- 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 3
- 150000001408 amides Chemical class 0.000 description 3
- 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 3
- 229960000723 ampicillin Drugs 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- 235000012208 gluconic acid Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 3
- 238000002744 homologous recombination Methods 0.000 description 3
- 230000006801 homologous recombination Effects 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 231100000219 mutagenic Toxicity 0.000 description 3
- 230000003505 mutagenic effect Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 102220005322 rs33959340 Human genes 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 235000008521 threonine Nutrition 0.000 description 3
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 2
- 102220624556 Actin, alpha skeletal muscle_E74K_mutation Human genes 0.000 description 2
- 108010031132 Alcohol Oxidoreductases Proteins 0.000 description 2
- 101000690713 Aspergillus niger Alpha-glucosidase Proteins 0.000 description 2
- 101000695691 Bacillus licheniformis Beta-lactamase Proteins 0.000 description 2
- 108010029675 Bacillus licheniformis alpha-amylase Proteins 0.000 description 2
- 101100479039 Caenorhabditis elegans aars-1 gene Proteins 0.000 description 2
- 241000222173 Candida parapsilosis Species 0.000 description 2
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000048120 Galactokinases Human genes 0.000 description 2
- 108700023157 Galactokinases Proteins 0.000 description 2
- 101100369308 Geobacillus stearothermophilus nprS gene Proteins 0.000 description 2
- 101100080316 Geobacillus stearothermophilus nprT gene Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 125000003440 L-leucyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C(C([H])([H])[H])([H])C([H])([H])[H] 0.000 description 2
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 2
- 241000218397 Magnolia x soulangeana Species 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- SBKRTALNRRAOJP-BWSIXKJUSA-N N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18R,21S)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1R)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6-methylheptanamide (6S)-N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18R,21S)-6,9,18-tris(2-aminoethyl)-15-benzyl-3-[(1R)-1-hydroxyethyl]-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6-methyloctanamide sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@@H](CCN)NC1=O)[C@@H](C)O.CC[C@H](C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@@H](NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@@H](CCN)NC1=O)[C@@H](C)O SBKRTALNRRAOJP-BWSIXKJUSA-N 0.000 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 2
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000002210 biocatalytic effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 102220353333 c.35C>T Human genes 0.000 description 2
- 229940055022 candida parapsilosis Drugs 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 108010061330 glucan 1,4-alpha-maltohydrolase Proteins 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 2
- 239000012139 lysis buffer Substances 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 150000008300 phosphoramidites Chemical class 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000011946 reduction process Methods 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 102220326689 rs1555494544 Human genes 0.000 description 2
- 102220005354 rs63749934 Human genes 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- OCUSNPIJIZCRSZ-ZTZWCFDHSA-N (2s)-2-amino-3-methylbutanoic acid;(2s)-2-amino-4-methylpentanoic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical compound CC(C)[C@H](N)C(O)=O.CC[C@H](C)[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O OCUSNPIJIZCRSZ-ZTZWCFDHSA-N 0.000 description 1
- FJLGEFLZQAZZCD-MCBHFWOFSA-N (3R,5S)-fluvastatin Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 FJLGEFLZQAZZCD-MCBHFWOFSA-N 0.000 description 1
- LXJXRIRHZLFYRP-VKHMYHEASA-L (R)-2-Hydroxy-3-(phosphonooxy)-propanal Natural products O=C[C@H](O)COP([O-])([O-])=O LXJXRIRHZLFYRP-VKHMYHEASA-L 0.000 description 1
- AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 1
- WGNSGQNASYNCBU-UHFFFAOYSA-N 4-bromo-3-hydroxybutanoic acid Chemical compound BrCC(O)CC(O)=O WGNSGQNASYNCBU-UHFFFAOYSA-N 0.000 description 1
- UCTNTYHJFWMUBD-UHFFFAOYSA-N 4-chloro-3-oxobutanoic acid Chemical class OC(=O)CC(=O)CCl UCTNTYHJFWMUBD-UHFFFAOYSA-N 0.000 description 1
- ADZQCEUEGXRCJY-UHFFFAOYSA-N 4-cyano-3-hydroxybutanoic acid Chemical compound N#CCC(O)CC(O)=O ADZQCEUEGXRCJY-UHFFFAOYSA-N 0.000 description 1
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 102000005751 Alcohol Oxidoreductases Human genes 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000534414 Anotopterus nikparini Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DJHGAFSJWGLOIV-UHFFFAOYSA-K Arsenate3- Chemical compound [O-][As]([O-])([O-])=O DJHGAFSJWGLOIV-UHFFFAOYSA-K 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 101000961203 Aspergillus awamori Glucoamylase Proteins 0.000 description 1
- 101900127796 Aspergillus oryzae Glucoamylase Proteins 0.000 description 1
- 101900318521 Aspergillus oryzae Triosephosphate isomerase Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 108090000145 Bacillolysin Proteins 0.000 description 1
- 101000775727 Bacillus amyloliquefaciens Alpha-amylase Proteins 0.000 description 1
- 241000194108 Bacillus licheniformis Species 0.000 description 1
- 241000194107 Bacillus megaterium Species 0.000 description 1
- 108010045681 Bacillus stearothermophilus neutral protease Proteins 0.000 description 1
- 101900040182 Bacillus subtilis Levansucrase Proteins 0.000 description 1
- 108091005658 Basic proteases Proteins 0.000 description 1
- 102100030981 Beta-alanine-activating enzyme Human genes 0.000 description 1
- 102100026189 Beta-galactosidase Human genes 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- 102100037633 Centrin-3 Human genes 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- LXJXRIRHZLFYRP-VKHMYHEASA-N D-glyceraldehyde 3-phosphate Chemical compound O=C[C@H](O)COP(O)(O)=O LXJXRIRHZLFYRP-VKHMYHEASA-N 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 101100342470 Dictyostelium discoideum pkbA gene Proteins 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101100385973 Escherichia coli (strain K12) cycA gene Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108090000698 Formate Dehydrogenases Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150108358 GLAA gene Proteins 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 241000193385 Geobacillus stearothermophilus Species 0.000 description 1
- 101100001650 Geobacillus stearothermophilus amyM gene Proteins 0.000 description 1
- 241000250507 Gigaspora candida Species 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101150009006 HIS3 gene Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 101100295959 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) arcB gene Proteins 0.000 description 1
- 101100246753 Halobacterium salinarum (strain ATCC 700922 / JCM 11081 / NRC-1) pyrF gene Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000773364 Homo sapiens Beta-alanine-activating enzyme Proteins 0.000 description 1
- 101000880522 Homo sapiens Centrin-3 Proteins 0.000 description 1
- 241001480714 Humicola insolens Species 0.000 description 1
- 241000235058 Komagataella pastoris Species 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
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 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
- 125000000769 L-threonyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])[C@](O[H])(C([H])([H])[H])[H] 0.000 description 1
- 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 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
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 125000003580 L-valyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(C([H])([H])[H])(C([H])([H])[H])[H] 0.000 description 1
- 108010059881 Lactase Proteins 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 101150068888 MET3 gene Proteins 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion 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](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) 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](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 1
- 101100022915 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cys-11 gene Proteins 0.000 description 1
- 108090000913 Nitrate Reductases Proteins 0.000 description 1
- 241001306288 Ophrys fuciflora Species 0.000 description 1
- 102000007981 Ornithine carbamoyltransferase Human genes 0.000 description 1
- 101710113020 Ornithine transcarbamylase, mitochondrial Proteins 0.000 description 1
- 102100037214 Orotidine 5'-phosphate decarboxylase Human genes 0.000 description 1
- 108010055012 Orotidine-5'-phosphate decarboxylase Proteins 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102000028391 RNA cap binding Human genes 0.000 description 1
- 108091000106 RNA cap binding Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 101000968489 Rhizomucor miehei Lipase Proteins 0.000 description 1
- 101100394989 Rhodopseudomonas palustris (strain ATCC BAA-98 / CGA009) hisI gene Proteins 0.000 description 1
- 101900354623 Saccharomyces cerevisiae Galactokinase Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 101100022918 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sua1 gene Proteins 0.000 description 1
- 102100032491 Serine protease 1 Human genes 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000256248 Spodoptera Species 0.000 description 1
- 241000228393 Sporidiobolus salmonicolor Species 0.000 description 1
- 241000222068 Sporobolomyces <Sporidiobolaceae> Species 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 101100309436 Streptococcus mutans serotype c (strain ATCC 700610 / UA159) ftf gene Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 241000187432 Streptomyces coelicolor Species 0.000 description 1
- 101100370749 Streptomyces coelicolor (strain ATCC BAA-471 / A3(2) / M145) trpC1 gene Proteins 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 101100157012 Thermoanaerobacterium saccharolyticum (strain DSM 8691 / JW/SL-YS485) xynB gene Proteins 0.000 description 1
- 241000223258 Thermomyces lanuginosus Species 0.000 description 1
- 241001313536 Thermothelomyces thermophila Species 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 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
- 101150050575 URA3 gene Proteins 0.000 description 1
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 108010045649 agarase Proteins 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 101150009206 aprE gene Proteins 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 101150008194 argB 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
- 229940000489 arsenate Drugs 0.000 description 1
- 210000004507 artificial chromosome Anatomy 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
- 229960005370 atorvastatin Drugs 0.000 description 1
- 101150103518 bar gene Proteins 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
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 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
- 239000003139 biocide Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- ZQNPDAVSHFGLIQ-UHFFFAOYSA-N calcium;hydrate Chemical compound O.[Ca] ZQNPDAVSHFGLIQ-UHFFFAOYSA-N 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000012219 cassette mutagenesis Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 229940106157 cellulase Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- WIVXEZIMDUGYRW-UHFFFAOYSA-L copper(i) sulfate Chemical compound [Cu+].[Cu+].[O-]S([O-])(=O)=O WIVXEZIMDUGYRW-UHFFFAOYSA-L 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 101150005799 dagA gene Proteins 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- XQGPKZUNMMFTAL-UHFFFAOYSA-L dipotassium;hydrogen phosphate;trihydrate Chemical compound O.O.O.[K+].[K+].OP([O-])([O-])=O XQGPKZUNMMFTAL-UHFFFAOYSA-L 0.000 description 1
- CDMADVZSLOHIFP-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane;decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 CDMADVZSLOHIFP-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- ZAJNMXDBJKCCAT-YFKPBYRVSA-N ethyl (3s)-4-chloro-3-hydroxybutanoate Chemical compound CCOC(=O)C[C@H](O)CCl ZAJNMXDBJKCCAT-YFKPBYRVSA-N 0.000 description 1
- AIZRKZQHJNWBEI-UHFFFAOYSA-N ethyl 4-bromo-3-hydroxybutanoate Chemical compound CCOC(=O)CC(O)CBr AIZRKZQHJNWBEI-UHFFFAOYSA-N 0.000 description 1
- ZAJNMXDBJKCCAT-UHFFFAOYSA-N ethyl 4-chloro-3-hydroxybutanoate Chemical compound CCOC(=O)CC(O)CCl ZAJNMXDBJKCCAT-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 101150019455 gdh gene Proteins 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
- 150000003944 halohydrins Chemical class 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 108010002685 hygromycin-B kinase Proteins 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 108010084715 isopropanol dehydrogenase (NADP) Proteins 0.000 description 1
- 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 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 229940116108 lactase Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 101150039489 lysZ gene Proteins 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- ISPYRSDWRDQNSW-UHFFFAOYSA-L manganese(II) sulfate monohydrate Chemical compound O.[Mn+2].[O-]S([O-])(=O)=O ISPYRSDWRDQNSW-UHFFFAOYSA-L 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 235000006109 methionine Nutrition 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000033607 mismatch repair Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 101150095344 niaD gene Proteins 0.000 description 1
- 229940101270 nicotinamide adenine dinucleotide (nad) Drugs 0.000 description 1
- 101150105920 npr gene Proteins 0.000 description 1
- 101150017837 nprM gene Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 108090000021 oryzin Proteins 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 101150019841 penP gene Proteins 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 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
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 1
- 108010082527 phosphinothricin N-acetyltransferase 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
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000002818 protein evolution Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 101150108007 prs gene Proteins 0.000 description 1
- 101150086435 prs1 gene Proteins 0.000 description 1
- 101150070305 prsA gene Proteins 0.000 description 1
- 238000002708 random mutagenesis Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000032537 response to toxin Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 102220207006 rs1057524249 Human genes 0.000 description 1
- 102220014369 rs145665265 Human genes 0.000 description 1
- 102220062022 rs150142859 Human genes 0.000 description 1
- 102220062248 rs568171603 Human genes 0.000 description 1
- 102220049651 rs59662841 Human genes 0.000 description 1
- 102220008752 rs6667 Human genes 0.000 description 1
- 102220227004 rs773552098 Human genes 0.000 description 1
- 101150025220 sacB gene Proteins 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000000176 sodium gluconate Substances 0.000 description 1
- 235000012207 sodium gluconate Nutrition 0.000 description 1
- 229940005574 sodium gluconate Drugs 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 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
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 101150016309 trpC gene Proteins 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
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 101150110790 xylB gene Proteins 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 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
- 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)
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49419503P | 2003-08-11 | 2003-08-11 | |
| US60/494,195 | 2003-08-11 | ||
| US54568204P | 2004-02-18 | 2004-02-18 | |
| US60/545,682 | 2004-02-18 | ||
| PCT/US2004/026655 WO2005017135A1 (en) | 2003-08-11 | 2004-08-11 | Improved ketoreductase polypeptides and related polynucleotides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2533838A1 true CA2533838A1 (en) | 2005-02-24 |
Family
ID=34197992
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002533838A Abandoned CA2533838A1 (en) | 2003-08-11 | 2004-08-11 | Improved ketoreductase polypeptides and related polynucleotides |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US7629157B2 (OSRAM) |
| EP (1) | EP1654354A1 (OSRAM) |
| JP (1) | JP2007502124A (OSRAM) |
| CA (1) | CA2533838A1 (OSRAM) |
| IL (1) | IL173191A (OSRAM) |
| WO (1) | WO2005017135A1 (OSRAM) |
Families Citing this family (129)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7125693B2 (en) | 2002-08-09 | 2006-10-24 | Codexis, Inc. | Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives |
| KR20060071397A (ko) | 2003-08-11 | 2006-06-26 | 코덱시스, 인코포레이티드 | 4-치환된 3-히드록시부티르산 유도체 및 이웃자리 시아노,히드록시 치환된 카르복실산 에스테르의 효소적 제조 방법 |
| KR20080036098A (ko) * | 2005-07-20 | 2008-04-24 | 가부시키가이샤 가네카 | 광학 활성 2-(ｎ-치환 아미노메틸)-3-히드록시부티르산에스테르류의 제조 방법 |
| AT502395B1 (de) * | 2005-07-27 | 2007-03-15 | Iep Gmbh | Oxidoreduktasen zur stereoselektiven reduktion von ketoverbindungen |
| WO2008100251A1 (en) | 2007-02-13 | 2008-08-21 | Ls9, Inc. | Modified microorganism uses therefor |
| DE102006010994A1 (de) * | 2006-03-09 | 2007-09-13 | Wacker Chemie Ag | Verfahren zur enzymatischen Herstellung von chiralen Alkoholen |
| AT503486B1 (de) * | 2006-04-11 | 2008-05-15 | Iep Gmbh | Verfahren zur enantioselektiven reduktion von steroiden |
| BRPI0712205A2 (pt) | 2006-05-19 | 2012-02-22 | Ls9, Inc. | Microorganismo, geneticamente modificado e métodos para produção melhorada de ácidos graxos, alcoís graxos, ésteres e cera de ácidos graxos usados em composições biocombustíveis, método para se obter um derivado de ácido graxo, composições biocombustíveis e biocombustiveis |
| US8110670B2 (en) | 2006-05-19 | 2012-02-07 | Ls9, Inc. | Enhanced production of fatty acid derivatives |
| US20100242345A1 (en) | 2006-05-19 | 2010-09-30 | LS9, Inc | Production of fatty acids & derivatives thereof |
| US7879585B2 (en) | 2006-10-02 | 2011-02-01 | Codexis, Inc. | Ketoreductase enzymes and uses thereof |
| WO2008103248A1 (en) * | 2007-02-08 | 2008-08-28 | Codexis, Inc. | Ketoreductases and uses thereof |
| AU2008230735A1 (en) | 2007-03-28 | 2008-10-02 | Ls9, Inc. | Enhanced production of fatty acid derivatives |
| EP2195443B1 (en) * | 2007-08-24 | 2015-01-07 | Codexis, Inc. | Improved ketoreductase polypeptides for the stereoselective production of (r)-3-hydroxythiolane |
| US8748143B2 (en) * | 2007-09-13 | 2014-06-10 | Codexis, Inc. | Ketoreductase polypeptides for the reduction of acetophenones |
| CN101889081B (zh) * | 2007-09-28 | 2014-06-18 | 科德克希思公司 | 酮还原酶多肽及其用途 |
| CN101883846A (zh) | 2007-10-01 | 2010-11-10 | 科德克希思公司 | 用于生成氮杂环丁酮的还原酶多肽 |
| WO2009045507A2 (en) * | 2007-10-03 | 2009-04-09 | Teva Pharmaceutical Industries Ltd. | Processes for preparing an intermediate of sitagliptin via enzymatic reduction |
| CN102015995B (zh) | 2008-03-03 | 2014-10-22 | 焦耳无限科技公司 | 产生碳基目的产物的二氧化碳固定工程微生物 |
| ES2575005T3 (es) | 2008-06-13 | 2016-06-23 | Codexis, Inc. | Método de síntesis de variantes de polinucleótidos |
| US20090312196A1 (en) | 2008-06-13 | 2009-12-17 | Codexis, Inc. | Method of synthesizing polynucleotide variants |
| AU2009271325A1 (en) | 2008-06-24 | 2010-01-21 | Merck Sharp & Dohme Corp. | Biocatalytic processes for the preparation of substantially stereomerically pure fused bicyclic proline compounds |
| WO2010025287A2 (en) | 2008-08-27 | 2010-03-04 | Codexis, Inc. | Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
| US8288131B2 (en) * | 2008-08-27 | 2012-10-16 | Codexis, Inc. | Ketoreductase polypeptides and uses thereof |
| SI2329013T1 (sl) | 2008-08-27 | 2016-03-31 | Codexis, Inc. | Polipeptidi ketoreduktaze za proizvodnjo 3-aril-3-hidroksipropanamina iz 3-aril-3-ketopropanamina |
| SG10201404330VA (en) | 2008-08-29 | 2014-10-30 | Codexis Inc | Ketoreductase Polypeptides For The Stereoselective Production Of (4S)-3[(5S)-5(4-Fluorophenyl)-5-Hydroxypentanoyl]-4-Phenyl-1,3-Oxazolidin-2-One |
| BRPI0914440A8 (pt) | 2008-10-17 | 2016-01-19 | Joule Unlimited Inc | Método para produção biogênica de etanol e cianobactéria geneticamente modificada |
| CA2747516C (en) | 2008-12-23 | 2019-11-05 | Ls9, Inc. | Methods and compositions related to thioesterase enzymes |
| WO2010081053A2 (en) | 2009-01-08 | 2010-07-15 | Codexis, Inc. | Transaminase polypeptides |
| CN102405281B (zh) | 2009-02-26 | 2015-05-13 | 科德克希思公司 | 转氨酶生物催化剂 |
| US8715996B2 (en) | 2009-02-26 | 2014-05-06 | Codexis, Inc. | Beta-glucosidase variant enzymes and related polynucleotides |
| US8263601B2 (en) | 2009-02-27 | 2012-09-11 | Concert Pharmaceuticals, Inc. | Deuterium substituted xanthine derivatives |
| CA2754580C (en) | 2009-03-17 | 2014-06-17 | Codexis, Inc. | Variant endoglucanases and related polynucleotides |
| EP2425007A4 (en) | 2009-04-27 | 2013-01-02 | Ls9 Inc | PREPARATION OF FATTY ACID ESTERS |
| EP2432890B1 (en) | 2009-05-22 | 2015-09-02 | Codexis, Inc. | Engineered biosynthesis of fatty alcohols |
| EP2446026B1 (en) | 2009-06-22 | 2017-08-09 | Codexis, Inc. | Transaminase reactions |
| HUE055413T2 (hu) * | 2009-06-22 | 2021-11-29 | Codexis Inc | Ketoreduktáz-közvetített sztereoszelektív útvonal alfa-klóralkoholokhoz |
| CN102471781B (zh) | 2009-06-30 | 2015-03-18 | 科德克希思公司 | 以脂肪醇形成酰基CoA还原酶(FAR)产生脂肪醇 |
| WO2011022548A2 (en) | 2009-08-19 | 2011-02-24 | Codexis, Inc. | Ketoreductase polypeptides for the preparation of phenylephrine |
| US20110082055A1 (en) * | 2009-09-18 | 2011-04-07 | Codexis, Inc. | Reduced codon mutagenesis |
| EP3301208B1 (en) | 2009-09-18 | 2020-11-04 | Codexis, Inc. | Reduced codon mutagenesis |
| EP2510089B1 (en) | 2009-12-08 | 2015-10-21 | Codexis, Inc. | Synthesis of prazole compounds |
| US9593326B2 (en) | 2009-12-09 | 2017-03-14 | Codexis, Inc. | Protein variant generation by region shuffling |
| US8986965B2 (en) | 2010-03-31 | 2015-03-24 | Codexis, Inc. | Production of monoterpenes |
| HUE026367T2 (en) | 2010-05-04 | 2016-06-28 | Codexis Inc | Biocatalysts for ezetimibe synthesis |
| WO2011145211A1 (ja) * | 2010-05-21 | 2011-11-24 | 明治製菓株式会社 | ケトレダクターゼ変異体 |
| DK2582799T3 (en) * | 2010-06-17 | 2018-02-12 | Codexis Inc | BIOCATALATORS AND PROCEDURES FOR THE SYNTHESIS OF (S) -3- (1-AMINOETHYL) -PHENOL |
| WO2012006114A2 (en) | 2010-06-28 | 2012-01-12 | Codexis, Inc. | Fatty alcohol forming acyl reductases (fars) and methods of use thereof |
| EP2605772B1 (en) | 2010-08-16 | 2016-06-22 | Cardiome International AG | Process for preparing aminocyclohexyl ether compounds |
| EP2606139B1 (en) | 2010-08-16 | 2015-07-15 | Codexis, Inc. | Biocatalysts and methods for the synthesis of (1r,2r)-2-(3,4-dimethoxyphenethoxy)cyclohexanamine |
| WO2012024662A2 (en) | 2010-08-20 | 2012-02-23 | Codexis, Inc. | Expression constructs comprising fungal promoters |
| US9085788B2 (en) | 2010-09-01 | 2015-07-21 | Concert Pharmaceuticals, Inc. | Process for preparing an enantiomerically enriched, deuterated secondary alcohol from a corresponding ketone without reducing deuterium incorporation |
| WO2012031073A1 (en) * | 2010-09-01 | 2012-03-08 | Concert Pharmaceuticals, Inc. | Process for preparing an enantiomerically enriched, deuterated secondary alcohol from a corresponding ketone without reducing deuterium incorporation |
| US9364797B2 (en) * | 2010-09-14 | 2016-06-14 | Council Of Scientific & Industrial Research | High flux hollow fiber ultrafiltration membranes and process for the preparation thereof |
| US20130289276A1 (en) * | 2010-10-08 | 2013-10-31 | Cadila Healthcare Limited | Process for preparing an intermediate of sitagliptin via enzymatic conversion |
| WO2012078800A2 (en) | 2010-12-08 | 2012-06-14 | Codexis, Inc. | Biocatalysts and methods for the synthesis of armodafinil |
| DK2697662T3 (en) | 2011-04-13 | 2018-07-30 | Codexis Inc | BIOCATALYTIC PROCEDURE FOR PREPARING ESLICARBAZEPIN AND ANALOGUES THEREOF |
| CN103998461B (zh) | 2011-09-08 | 2018-02-02 | 科德克希思公司 | 用于合成取代的内酰胺的生物催化剂和方法 |
| CA2852810A1 (en) * | 2011-10-19 | 2013-04-25 | Cipla Limited | Process for the preparation of an endothelin receptor antagonist |
| EP2780448B1 (en) | 2011-11-18 | 2019-09-11 | Codexis, Inc. | Biocatalysts for the preparation of hydroxy substituted carbamates |
| EP2794893A4 (en) | 2011-12-20 | 2015-08-12 | Codexis Inc | PRODUCTION OF SATURATED FATTY ALCOHOLS FROM GENETICALLY MODIFIED MICROORGANISMS |
| KR102057590B1 (ko) | 2012-03-23 | 2019-12-19 | 노파르티스 아게 | 스피로인돌론을 제조하기 위한 화학적 방법 및 그의 중간체 |
| US9139821B2 (en) | 2012-03-23 | 2015-09-22 | Codexis, Inc. | Biocatalysts and methods for synthesizing derivatives of tryptamine and tryptamine analogs |
| US20150133698A1 (en) | 2012-04-20 | 2015-05-14 | Codexis, Inc. | Production of fatty alcohols from engineered microorganisms |
| DK2847327T3 (en) | 2012-05-08 | 2019-03-11 | Codexis Inc | BIO-CATALYSTS AND METHODS FOR HYDROXYLATION OF CHEMICAL COMPOUNDS |
| CN107904216B (zh) | 2012-05-11 | 2021-06-29 | 科德克希思公司 | 工程化亚胺还原酶以及用于酮和胺化合物的还原胺化的方法 |
| US9650655B2 (en) | 2012-07-20 | 2017-05-16 | Codexis, Inc. | Production of fatty alcohols from engineered microorganisms |
| US9512447B2 (en) | 2012-12-14 | 2016-12-06 | Codexis, Inc. | Modified native beta-ketoacyl-ACP synthases and engineered microorganisms |
| DK2935572T3 (da) | 2012-12-21 | 2020-11-16 | Codexis Inc | Modificerede biokatalysatorer og fremgangsmåder til syntetisering af chirale aminer |
| CA2898495C (en) | 2013-01-18 | 2021-06-01 | Codexis, Inc. | Engineered biocatalysts useful for carbapenem synthesis |
| CA2902824C (en) | 2013-02-28 | 2021-06-22 | Codexis, Inc. | Engineered transaminase polypeptides for industrial biocatalysis |
| WO2014150633A1 (en) | 2013-03-15 | 2014-09-25 | Merck Sharp & Dohme Corp. | Immobilized ketoreductases and process for making and using immobilized ketoreductase |
| EP2986724B1 (en) * | 2013-04-17 | 2018-10-03 | Council of Scientific & Industrial Research | Designer cells for enantioselective reduction of ketones and use thereof in efficient production of enantioenriched alcohols |
| EP3068793B1 (en) | 2013-11-13 | 2021-02-17 | Codexis, Inc. | Engineered imine reductases and methods for the reductive amination of ketone and amine compounds |
| US9133488B2 (en) | 2013-12-30 | 2015-09-15 | University Of Alaska Fairbanks | Synthetic methods and compounds related thereto |
| CN106536725A (zh) | 2014-04-22 | 2017-03-22 | C-乐克塔股份有限公司 | 酮还原酶 |
| EP3256577B1 (en) | 2015-02-10 | 2020-08-26 | Codexis, Inc. | Ketoreductase polypeptides for the synthesis of chiral compounds |
| CN104659287B (zh) * | 2015-03-12 | 2017-05-31 | 京东方科技集团股份有限公司 | 像素界定层及制备方法、显示基板及制备方法、显示装置 |
| AU2016258091B2 (en) | 2015-05-07 | 2020-10-01 | Codexis, Inc. | Penicillin-G acylases |
| MX389364B (es) | 2016-05-05 | 2025-03-19 | Codexis Inc | Penicilina g acilasas |
| US10184117B2 (en) | 2016-06-09 | 2019-01-22 | Codexis, Inc. | Biocatalysts and methods for hydroxylation of chemical compounds |
| MX2018015534A (es) | 2016-06-15 | 2019-03-14 | Codexis Inc | Beta-glucosidasas dise?adas y metodos de glucosilacion. |
| JP7316662B2 (ja) | 2016-08-26 | 2023-07-28 | コデクシス， インコーポレイテッド | 操作されたイミンレダクターゼ、ならびにケトン化合物およびアミン化合物の還元的アミノ化のための方法 |
| EP3565893A4 (en) | 2017-01-05 | 2020-12-09 | Codexis, Inc. | PENICILLIN G ACYLASES |
| AU2018215335B2 (en) | 2017-02-03 | 2020-10-01 | Tate & Lyle Solutions Usa Llc | Engineered glycosyltransferases and steviol glycoside glucosylation methods |
| IL270091B2 (en) | 2017-04-27 | 2025-08-01 | Codexis Inc | Ketoroductase polypeptides and polynucleotides |
| PL3635101T3 (pl) | 2017-05-08 | 2021-12-13 | Codexis, Inc. | Poddane inżynierii warianty ligazy |
| JP7122009B2 (ja) | 2017-06-14 | 2022-08-19 | コデクシス， インコーポレイテッド | 産業上の生体触媒作用のための操作されたトランスアミナーゼポリペプチド |
| CN111051506B (zh) | 2017-06-27 | 2023-11-24 | 科德克希思公司 | 青霉素g酰化酶 |
| AU2018292104B2 (en) | 2017-06-30 | 2025-03-27 | Codexis, Inc. | T7 RNA polymerase variants |
| KR102773542B1 (ko) | 2017-06-30 | 2025-02-25 | 코덱시스, 인코포레이티드 | T7 rna 폴리머라제 변이체 |
| EP3652328A1 (en) | 2017-07-14 | 2020-05-20 | c-LEcta GmbH | Ketoreductases |
| WO2019094301A1 (en) | 2017-11-07 | 2019-05-16 | Codexis, Inc. | Transglutaminase variants |
| JP2021506252A (ja) | 2017-12-13 | 2021-02-22 | コデクシス， インコーポレイテッド | アミドカップリングのためのカルボキシエステラーゼポリペプチド |
| ES3018269T3 (en) | 2017-12-13 | 2025-05-14 | Glaxosmithkline Ip Dev Ltd | Carboxyesterase biocatalysts |
| GB201802383D0 (en) * | 2018-02-14 | 2018-03-28 | Givaudan Sa | Process |
| ES2975412T3 (es) | 2018-06-21 | 2024-07-05 | Fis Fabbrica Italiana Sintetici Spa | Proceso enzimático para la preparación de droxidopa |
| KR20210032417A (ko) | 2018-07-09 | 2021-03-24 | 코덱시스, 인코포레이티드 | 조작된 데옥시리보스-포스페이트 알돌라아제 |
| KR20210032950A (ko) | 2018-07-16 | 2021-03-25 | 노파르티스 아게 | 페닐피페리디닐 인돌 유도체를 제조하기 위한 화학적 방법 |
| BR112021001661A8 (pt) | 2018-07-30 | 2022-08-09 | Codexis Inc | Glicosiltransferase modificada, polinucleotídeo modificado, vetor, célula hospedeira, métodos para produzir pelo menos uma glicosiltransferase modificada, para produzir pelo menos uma variante de sacarose sintase, para glicosilação de um substrato, para produzir rebaudiosídeo m, rebaudiosídeo a e/ou rebaudiosídeo i e rebaudiosídeo d, composição, sacarose sintase modificada, pelo menos um rebaudiosídeo, rebaudiosídeo m, rebaudiosídeo a, rebaudiosídeo i, e, rebaudiosídeo d. |
| KR102602138B1 (ko) | 2018-09-26 | 2023-11-13 | 칼라마주 홀딩스, 인크. | 개질된 홉 생성물의 제조를 위한 효소적 방법 |
| CA3117879A1 (en) * | 2018-10-26 | 2020-04-30 | Tami Bar | Compositions and methods for biodegrading alcohol |
| CN113316635A (zh) | 2018-10-29 | 2021-08-27 | 科德克希思公司 | 工程化dna聚合酶变体 |
| AU2019397401A1 (en) | 2018-12-14 | 2021-06-17 | Codexis, Inc. | Engineered tyrosine ammonia lyase |
| WO2020150125A1 (en) | 2019-01-15 | 2020-07-23 | Codexis, Inc. | Engineered transaminase polypeptides |
| US12215359B2 (en) | 2019-05-01 | 2025-02-04 | Codexis, Inc. | Engineered glucose dehydrogenases and methods for the reductive amination of ketone and amine compounds |
| WO2020223102A1 (en) | 2019-05-01 | 2020-11-05 | Codexis, Inc. | Engineered imine reductases and methods for the reductive amination of ketone and amine compounds |
| US12173345B2 (en) | 2019-06-13 | 2024-12-24 | Asymchem Laboratories (Tianjin) Co., Ltd. | Ketoreductase mutant and method for producing chiral alcohols |
| JP7678580B2 (ja) | 2019-07-02 | 2025-05-16 | コデクシス， インコーポレイテッド | 操作されたスクロースホスホリラーゼバリアント酵素 |
| MX2022002473A (es) | 2019-08-30 | 2022-08-02 | Codexis Inc | Variantes de lipasa modificadas geneticamente. |
| JP2022547523A (ja) | 2019-09-12 | 2022-11-14 | コデクシス， インコーポレイテッド | １０－アセチル－３，７－ジヒドロキシフェノキサジンに対するペルオキシダーゼ活性 |
| EP4063512A4 (en) * | 2019-11-22 | 2024-01-03 | API Corporation | CARBONYL REDUCTASE, NUCLEIC ACID ENCODING SAME, AND METHOD FOR PRODUCING AN OPTICALLY ACTIVE COMPOUND USING SAME |
| JP7720098B2 (ja) | 2019-11-26 | 2025-08-07 | コデクシス， インコーポレイテッド | 化合物のヒドロキシル化のための生体触媒および方法 |
| MX2022009531A (es) | 2020-02-04 | 2022-09-09 | Codexis Inc | Leucina descarboxilasas modificadas geneticamente. |
| JP2023521772A (ja) | 2020-04-10 | 2023-05-25 | コデクシス， インコーポレイテッド | 操作されたトランスアミナーゼポリペプチド |
| EP4204552A4 (en) | 2020-08-28 | 2024-10-16 | Codexis, Inc. | Engineered amylase variants |
| CN117098847A (zh) | 2020-08-28 | 2023-11-21 | 科德克希思公司 | 工程化蛋白酶变体 |
| WO2022066155A1 (en) | 2020-09-24 | 2022-03-31 | Kalamazoo Holdings, Inc. | Enzymatic process for production of modified hop products |
| CN112410276B (zh) * | 2020-11-27 | 2023-03-21 | 江苏阿尔法药业股份有限公司 | 一种2-氯-1-(3,4-二氟苯基)乙酮还原酶重组菌株及构建方法和应用 |
| EP4262804A4 (en) | 2020-12-18 | 2025-02-12 | Codexis, Inc. | Engineered uridine phosphorylase variant enzymes |
| AU2022279241A1 (en) | 2021-05-21 | 2023-11-30 | Codexis, Inc. | Engineered methionine gamma lyase variants |
| US20250136954A1 (en) * | 2021-08-13 | 2025-05-01 | Codexis, Inc. | Engineered nucleoside deoxyribosyltransferase variant enzymes |
| JP2024539636A (ja) | 2021-10-15 | 2024-10-29 | コデクシス， インコーポレイテッド | 操作されたｄｎａポリメラーゼバリアント |
| WO2023077169A2 (en) | 2021-11-01 | 2023-05-04 | Codexis, Inc. | Engineered leucine decarboxylases |
| CN119698468A (zh) | 2022-08-26 | 2025-03-25 | 特沙诺有限公司 | 生物催化剂及其方法 |
| AR131406A1 (es) | 2022-12-20 | 2025-03-19 | Novartis Ag | Método de ligación de ácidos nucleicos |
| AR131405A1 (es) | 2022-12-20 | 2025-03-19 | Novartis Ag | Ligasas modificadas y usos de las mismas |
| EP4649143A1 (en) | 2023-01-12 | 2025-11-19 | Novartis AG | Engineered ketoreductase polypeptides |
| WO2025235589A1 (en) | 2024-05-08 | 2025-11-13 | Codexis, Inc. | Dna polymerase variants |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9512837D0 (en) | 1995-06-23 | 1995-08-23 | Zeneca Ltd | reduction of ketone groups |
| DE69731317T2 (de) * | 1997-02-07 | 2006-02-23 | Kaneka Corp. | Neue carbonyl-reduktase, gene welche diese kodieren und methoden zu deren verwendung |
| US6531308B2 (en) | 1997-11-04 | 2003-03-11 | Eli Lilly And Company | Ketoreductase gene and protein from yeast |
| AU1302999A (en) * | 1997-11-04 | 1999-05-24 | Eli Lilly And Company | Ketoreductase gene and protein from yeast |
| WO1999032434A1 (en) | 1997-12-19 | 1999-07-01 | Warner-Lambert Export Limited | Process for the synthesis of 1,3-diols |
| CA2329893A1 (en) | 1998-04-30 | 1999-11-11 | Kaneka Corporation | Process for producing 6-cyanomethyl-1,3-dioxane-4-acetic acid derivatives |
| DE69937374T2 (de) | 1998-08-05 | 2008-07-24 | Kaneka Corp. | Verfahren zur Herstellung von 3,5-dihydroxy substituierten Estern als Zwischenprodukte zur Herstellung optisch aktiver 2-(6-(Hydroxymethyl)-1,3-dioxan-4-yl)-essigsäure-Derivate |
| MXPA01004786A (es) | 1998-11-12 | 2002-09-18 | Larry Kirn | Amplificador de conmutacion de alta exactitud, con referencia multiple. |
| WO2001004336A1 (de) | 1999-07-09 | 2001-01-18 | Forschungszentrum Jülich GmbH | Verfahren zur reduktion von keto-carbonsäuren und deren estern |
| KR100512080B1 (ko) | 1999-12-03 | 2005-09-02 | 카네카 코포레이션 | 신규 카르보닐 환원효소, 그의 유전자, 및 그의 이용 방법 |
| US6492868B2 (en) | 2000-08-14 | 2002-12-10 | Larry Kirn | Dynamic range enhancement technique |
| IL159368A0 (en) | 2001-07-02 | 2004-06-01 | Kaneka Corp | Method of modifying enzyme and oxidoreductase variant |
| WO2003078615A1 (en) | 2002-03-18 | 2003-09-25 | Ciba Specialty Chemicals Holding Inc. | Alcohol dehydrogenases with high solvent and temperature stability |
| US7125693B2 (en) * | 2002-08-09 | 2006-10-24 | Codexis, Inc. | Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives |
| KR20060071397A (ko) * | 2003-08-11 | 2006-06-26 | 코덱시스, 인코포레이티드 | 4-치환된 3-히드록시부티르산 유도체 및 이웃자리 시아노,히드록시 치환된 카르복실산 에스테르의 효소적 제조 방법 |
| DE102004029112B4 (de) | 2004-06-11 | 2007-06-21 | Julich Chiral Solutions Gmbh | Alkoholdehydrogenase zur stereoselektiven Gewinnung von Hydroxyverbindungen |
-
2004
- 2004-08-11 WO PCT/US2004/026655 patent/WO2005017135A1/en not_active Ceased
- 2004-08-11 JP JP2006523448A patent/JP2007502124A/ja active Pending
- 2004-08-11 EP EP04781365A patent/EP1654354A1/en not_active Withdrawn
- 2004-08-11 CA CA002533838A patent/CA2533838A1/en not_active Abandoned
- 2004-08-11 US US10/916,311 patent/US7629157B2/en active Active
-
2006
- 2006-01-17 IL IL173191A patent/IL173191A/en not_active IP Right Cessation
-
2009
- 2009-10-08 US US12/576,195 patent/US7833767B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US20060195947A1 (en) | 2006-08-31 |
| IL173191A0 (en) | 2006-06-11 |
| EP1654354A1 (en) | 2006-05-10 |
| WO2005017135A1 (en) | 2005-02-24 |
| US7629157B2 (en) | 2009-12-08 |
| IL173191A (en) | 2010-12-30 |
| JP2007502124A (ja) | 2007-02-08 |
| US7833767B2 (en) | 2010-11-16 |
| WO2005017135A8 (en) | 2012-06-14 |
| US20100028972A1 (en) | 2010-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7629157B2 (en) | Ketoreductase polypeptides and related polynucleotides | |
| EP1660648B1 (en) | Improved glucose dehydrogenase polypeptides and related polynucleotides | |
| EP2115130B1 (en) | Ketoreductases and uses thereof | |
| US20250327042A1 (en) | Novel p450-bm3 variants with improved activity | |
| KR20210030379A (ko) | 조작된 갈락토스 옥시다제 변이 효소 | |
| EP3319987B1 (en) | Novel p450-bm3 variants with improved activity | |
| US7790432B2 (en) | Alanine 2,3-aminomutases and related polynucleotides | |
| CN114760980B (zh) | 针对10-乙酰基-3,7-二羟基吩噁嗪的过氧化物酶活性 | |
| US8030051B2 (en) | Alanine 2,3-aminomutases and related polynucleotides | |
| AU2021102284A4 (en) | Peptide linker, fusion protein comprising the peptide linker and uses thereof | |
| WO2024010785A1 (en) | Ketoreductase enzymes for the synthesis of 1,3-diol substituted indanes | |
| WO2007028729A1 (en) | Nocardia globerula alcohol dehydrogenase and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |