羰基还原酶及其催化不对称合成大基团手性羟基类化合物的研究进展
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摘要
手性羟基化合物以其独特的光、热和化学性质广泛应用于医药、农药、精细化工、功能材料等行业.立体专一性羰基还原酶能够直接针对关键手性位点催化不对称还原潜手性底物获得目的手性产物.基于羰基还原酶的底物多样性,具有不同化学结构和功能的醇类、酯类、氨基酸、环氧化合物等重要手性中间体能够通过不对称还原途径实现单一光学活性对映体的高效制备.然而,针对具有应用价值的含有大基团、结构复杂的潜手性羰基化合物,已知的羰基还原酶通常催化活性较低.本文综述了生物催化不对称氧化还原反应的特点和规律及其关键立体选择性羰基还原酶的性质和结构特征,并在此基础上,重点针对大基团手性羟基化合物的不对称合成,总结了羰基还原酶及其催化系统开发和应用的研究进展,并进一步提出解决该关键问题的主要发展策略.
Chiral hydroxyl compounds have been widely used in pharmaceutical, agrochemical, fine chemicals, and functional materials industries, due to their unique physical and chemical properties. Stereoselective carbonyl reductases can be efficiently applied to catalyze asymmetric synthesis of chiral hydroxyl compounds with high optical purity from directed reduction of prochiral carbonyl group of the corresponding keto substrates. Based on the diversity of substrates, single enantiomers of various chiral hydroxyl compounds, including chiral alcohols, hydroxyl esters, and hydroxyl amino acids, can be prepared through carbonyl reductasecatalyzed asymmetric reduction in a high efficiency. However, most of the available carbonyl reductases only exhibit low activity towards the substrates involving bulky groups. This review summarizes the basic traits and principles of biocatalytic asymmetric oxidoreductions, and the key characteristics and structure-function relationship of stereoselective carbonyl reductases. In addition, the carbonyl reductases and their systems for asymmetric synthesis of bulky chiral hydroxyl compounds are also addressed, and the potential strategies targeting the critical issue are further discussed.
Chiral hydroxyl compounds have been widely used in pharmaceutical, agrochemical, fine chemicals, and functional materials industries, due to their unique physical and chemical properties. Stereoselective carbonyl reductases can be efficiently applied to catalyze asymmetric synthesis of chiral hydroxyl compounds with high optical purity from directed reduction of prochiral carbonyl group of the corresponding keto substrates. Based on the diversity of substrates, single enantiomers of various chiral hydroxyl compounds, including chiral alcohols, hydroxyl esters, and hydroxyl amino acids, can be prepared through carbonyl reductasecatalyzed asymmetric reduction in a high efficiency. However, most of the available carbonyl reductases only exhibit low activity towards the substrates involving bulky groups. This review summarizes the basic traits and principles of biocatalytic asymmetric oxidoreductions, and the key characteristics and structure-function relationship of stereoselective carbonyl reductases. In addition, the carbonyl reductases and their systems for asymmetric synthesis of bulky chiral hydroxyl compounds are also addressed, and the potential strategies targeting the critical issue are further discussed.
引文
1 McCoy M.Business concentrates:Johnson Matthey buys biocatalysis company.Chem Eng News,2010,88:20
2 Hartwig J.Recipes for excess.Nature,2005,437:487-488
3 Thayer A M.Enzymes at work.Chem Eng News,2006,84:15-25
4 Schmid A,Dordick J S,Hauer B,et al.Industrial biocatalysis today and tomorrow.Nature,2001,409:258-268
5 Thayer A M.Biocatalysis helps reach a resolution.Chem Eng News,2006,84:29-31
6 Hall M,Bommarius A S.Enantioenriched compounds via enzyme-catalyzed redox reactions.Chem Rev,2011,111:4088-4110
7 Noyori R.Asymmetric catalysis:Science and opportunities(nobel lecture).Angew Chem Int Ed,2002,41:2008-2022
8 Kroutil W,Mang H,Edegger K,et al.Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols.Curr Opin Chem Biol,2004,8:120-126
9 Schoemaker H E,Mink D,Wubbolts M G.Dispelling the myths-biocatalysis in industrial synthesis.Science,2003,299:1694-1697
10 Matsuda T,Yamanaka R,Nakamura K.Recent progress in biocatalysis for asymmetric oxidation and reduction.Tetrahedron-Asymmetry,2009,20:513-557
11 Hummel W.Large-scale applications of NAD(P)-dependent oxidoreductases:Recent developments.Trends Biotech,1999,17:487-492
12 Hollmann F,Arends I W C E,Holtmann D.Enzymatic reductions for the chemist.Green Chem,2011,13:2285-2314
13 Pennacchio A,Giordano A,Pucci B,et al.Biochemical characterization of a recombinant short-chain NAD(H)-dependent dehydrogenase/reductase from Sulfolobus acidocaldarius.Extremophiles,2010,14:193-204
14 Kavanagh K L,J?rnvall H,Persson B,et al.Medium-and short-chain dehydrogenase/reductase gene and protein families.Cell Mol Life Sci,2008,65:3895-3906
15 Knoll M,Pleiss J.The Medium-chain dehydrogenase/reductase engineering database:A systematic analysis of a diverse protein family to understand sequence-structure-function relationship.Protein Sci,2008,17:1689-1697
16 Hyndman D,Bauman D R,Heredia V V,et al.The aldo-keto reductase superfamily homepage.Chemico-Biol Interact,2003,143-144:621-631
17 Jez J M,Bennett M J,Schlegel B P,et al.Comparative anatomy of the aldo-keto reductase superfamily.Biochem J,1997,326:625-636
18 Couture J F,Legrand P,Cantin L,et al.Loop relaxation,a mechanism that explains the reduced specificity of rabbit 20α-hydroxysteroid dehydrogenase,a member of the aldo-keto reductase superfamily.J Mol Biol,2004,339:89-102
19 Kizaki N,Yasohara Y,Nagashima N,et al.Characterization of novel alcohol dehydrogenase of Devosia riboflavina involved in stereoselective reduction of 3-pyrrolidinone derivatives.J Mol Catal B-Enzym,2008,51:73-80
20 Yamada-Onodera K,Kojima K,Takase Y,et al.Cloning,sequence analysis,and expression in Escherichia coli of gene encoding N-benzyl-3-pyrrolidinol dehydrogenase from Geotrichum capitatum.J Biosci Bioeng,2007,104:379-384
21 Liang J,Lalonde J,Borup B,et al.Development of a biocatalytic process as an alternative to the(-)-DIP-Cl-mediated asymmetric reduction of a key intermediate of montelukast.Org Proc Res Dev,2009,14:193-198
22 Nie Y,Wang S,Xu Y,et al.Enzyme engineering based on X-ray structures and kinetic profiling of substrate libraries:alcohol dehydrogenases for stereospecific synthesis of a broad range of chiral alcohols.ACS Catal,2018,8:5145-5152
23 Lavandera I,Kern A,Ferreira-Silva B,et al.Stereoselective bioreduction of bulky-bulky ketones by a novel ADH from Ralstonia sp..J Org Chem,2008,73:6003-6005
24 Athanasiou N,Smallridge A J,Trewhella M A.Baker’s yeast mediated reduction ofβ-keto esters andβ-keto amides in an organic solvent system.J Mol Catal B-Enzym,2001,11:893-896
25 Hummel W.New alcohol dehydrogenases for the synthesis of chiral compounds.New Enzym Org Syn,1997,58:145-184
26 Naik H G,Yeniad B,Koning C E,et al.Investigation of asymmetric alcohol dehydrogenase(ADH)reduction of acetophenone derivatives:Effect of charge density.Org Biomol Chem,2012,10:4961-4967
27 Zhu D,Hua L.Enantioselective enzymatic reductions of sterically bulky aryl alkyl ketones catalyzed by a NADPH-dependent carbonyl reductase.J Org Chem,2006,71:9484-9486
28 K?dziora K,Díaz-Rodríguez A,Lavandera I,et al.Laccase/TEMPO-mediated system for the thermodynamically disfavored oxidation of 2,2-dihalo-1-phenylethanol derivatives.Green Chem,2014,16:2448-2453
29 Ishihara K,Kato C,Yamaguchi H,et al.Stereoselective reduction of carbonyl compounds with actinomycete:purification and characterization of threeα-keto ester reductases from Streptomyces avermitilis.Biosci Biotech Biochem,2008,72:3249-3257
30 Yamaguchi H,Nakajima N,Ishihara K.Purification and characterization of twoα-keto ester reductases from Streptomyces thermocyaneoviolaceus IFO 14271.Biosci Biotech Biochem,2002,66:588-597
31 Yadav G D,Sajgure A D,Dhoot S B.Insight into microwave irradiation and enzyme catalysis in enantioselective resolution of RS-(±)-methyl mandelate.J Chem Technol Biotechnol,2008,83:1145-1153
32 Guo J L,Mu X Q,Xu Y.Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of(R)-methyl mandelate.Bioprocess Biosyst Eng,2010,33:797-804
33 Kasprzak J,Rauter M,Denter S,et al.Synthesis of ethyl(R)-mandelate using recombinant carboxydothermus hydrogenoformans alcohol dehydrogenase produced by two yeast species.J Mol Catal B-Enzym,2016,133:176-186
34 Milagre H M S,Milagre C D F,Moran P J S,et al.Reduction of ethyl benzoylformate mediated by Saccharomyces cerevisiae entrapped in alginate fibers with double gel layers in a continuously operated reactor.Enzyme Microbial Tech,2005,37:121-125
35 Nikaido T,Matsuyama A,Ito M,et al.Stereospecific reduction of 2-oxo-4-phenylbutanoate to(R)-2-hydroxy-4-phenylbutanoate with microbial cells.Biosci Biotech Biochem,2014,56:2066-2067
36 de Lacerda P S B,Ribeiro J B,Leite S G F,et al.Microbial reduction of ethyl 2-oxo-4-phenylbutyrate.Searching for R-enantioselectivity.New access to the enalapril like ACE inhibitors.Tetrahedron-Asymmetry,2006,17:1186-1188
37 Ni Y,Li C X,Ma H M,et al.Biocatalytic properties of a recombinant aldo-keto reductase with broad substrate spectrum and excellent stereoselectivity.Appl Microbiol Biotechnol,2010,89:1111-1118
38 Oda S,Inada Y,Kobayashi A,et al.Production of ethyl(R)-2-hydroxy-4-phenylbutanoate via reduction of ethyl 2-oxo-4-phenylbutanoate in an interface bioreactor.Biosci Biotech Biochem,2014,62:1762-1767
39 Lacerda P S B,Ribeiro J B,Leite S G F,et al.Microbial enantioselective reduction of ethyl-2-oxo-4-phenyl-butanoate.Biochem Eng J,2006,28:299-302
40 Zhang W,Ni Y,Sun Z,et al.Biocatalytic synthesis of ethyl(R)-2-hydroxy-4-phenylbutyrate with Candida krusei SW2026:A practical process for high enantiopurity and product titer.Process Biochem,2026,44:1270-1275
41 Ou Z,Chen X,Ying G,et al.Continuous preparation of(S)-3-hydroxy-3-phenylpropionate by asymmetric reduction of 3-oxo-3-phenylpropionic acid ethyl ester with Saccharomyces cerevisiae CGMCC No.2266 in a membrane reactor.Biotechnol Bioproc E,2011,16:320-326
42 Wang P Y,Tsai S W.Hydrolytic resolution of(R,S)-3-hydroxy-3-phenylpropionates by esterase from Klebsiella oxytoca:Effects of leaving alcohol,covalent immobilization and aqueous pH.J Mol Catal B-Enzymatic,2009,59:70-75
43 Engelking H,Pfaller R,Wich G,et al.Reaction engineering studies onβ-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae.Enzyme Microbial Tech,2006,38:536-544
44 Chen J,Yan M,Xu L.Efficient synthesis of(S)-N-Boc-3-hydroxypiperidine using an(R)-specific carbonyl reductase from Candida parapsilosis.World J Microbiol Biotechnol,2017,33:61-72
45 Yamada-Onodera K,Fukui M,Tani Y.Purification and characterization of alcohol dehydrogenase reducing N-benzyl-3-pyrrolidinone from Geotrichum capitatum.J Biosci Bioeng,2007,103:174-178
46 Liu H,Hoff B H,Anthonsen T.Chemo-enzymatic synthesis of the antidepressant duloxetine and its enantiomer.Chirality,2000,12:26-29
47 Soni P,Banerjee U C.Biotransformations for the production of the chiral drug(S)-duloxetine catalyzed by a novel isolate of Candida tropicalis.Appl Microbiol Biotechnol,2005,67:771-777
48 Gong X M,Qin Z,Li F L,et al.Development of an engineered ketoreductase with simultaneously improved thermostability and activity for making a bulky atorvastatin precursor.ACS Catal,2019,9:147-153
49 Liu Z Q,Wu L,Zhang X J,et al.Directed evolution of carbonyl reductase from Rhodosporidium toruloides and its application in stereoselective synthesis of tert-butyl(3R,5S)-6-chloro-3,5-dihydroxyhexanoate.J Agric Food Chem,2017,65:3721-3729
50 Xu G C,Shang Y P,Yu H L,et al.Identification of key residues in Debaryomyces hansenii carbonyl reductase for highly productive preparation of(S)-aryl halohydrins.Chem Commun,2015,51:15728-15731
51 Huang L,Ma H M,Yu H L,et al.Altering the substrate specificity of reductase Cg KR1 from Candida glabrata by protein engineering for bioreduction of aromaticα-keto esters.Adv Synth Catal,2014,356:1943-1948
52 Zheng G W,Liu Y Y,Chen Q,et al.Preparation of structurally diverse chiral alcohols by engineering ketoreductase Cg KR1.ACS Catal,2017,7:7174-7181
53 Li A,Ye L,Yang X,et al.Reconstruction of the catalytic pocket and enzyme-substrate interactions to enhance the catalytic efficiency of a shortchain dehydrogenase/reductase.ChemCatChem,2016,8:3229-3233
54 Qu G,Zhang K,Jiang Y,et al.The Nobel Prize in Chemistry 2018:the directed evolution of enzyme and the phage display technologies(in Chinese).J Biol,2019,36:1-6,19[曲戈,张锟,蒋迎迎,等.2018诺贝尔化学奖:酶定向进化与噬菌体展示技术.生物学杂志,2019,36:1-6,19]
55 Parkot J,Gr?ger H,Hummel W.Purification,cloning,and overexpression of an alcohol dehydrogenase from Nocardia globerula reducing aliphatic ketones and bulky ketoesters.Appl Microbiol Biotechnol,2010,86:1813-1820
56 Liang C,Nie Y,Mu X,et al.Gene mining-based identification of aldo-keto reductases for highly stereoselective reduction of bulky ketones.Bioresour Bioprocess,2018,5:33
57 Li R,Wijma H J,Song L,et al.Computational redesign of enzymes for regio-and enantioselective hydroamination.Nat Chem Biol,2018,14:664-670
2 Hartwig J.Recipes for excess.Nature,2005,437:487-488
3 Thayer A M.Enzymes at work.Chem Eng News,2006,84:15-25
4 Schmid A,Dordick J S,Hauer B,et al.Industrial biocatalysis today and tomorrow.Nature,2001,409:258-268
5 Thayer A M.Biocatalysis helps reach a resolution.Chem Eng News,2006,84:29-31
6 Hall M,Bommarius A S.Enantioenriched compounds via enzyme-catalyzed redox reactions.Chem Rev,2011,111:4088-4110
7 Noyori R.Asymmetric catalysis:Science and opportunities(nobel lecture).Angew Chem Int Ed,2002,41:2008-2022
8 Kroutil W,Mang H,Edegger K,et al.Recent advances in the biocatalytic reduction of ketones and oxidation of sec-alcohols.Curr Opin Chem Biol,2004,8:120-126
9 Schoemaker H E,Mink D,Wubbolts M G.Dispelling the myths-biocatalysis in industrial synthesis.Science,2003,299:1694-1697
10 Matsuda T,Yamanaka R,Nakamura K.Recent progress in biocatalysis for asymmetric oxidation and reduction.Tetrahedron-Asymmetry,2009,20:513-557
11 Hummel W.Large-scale applications of NAD(P)-dependent oxidoreductases:Recent developments.Trends Biotech,1999,17:487-492
12 Hollmann F,Arends I W C E,Holtmann D.Enzymatic reductions for the chemist.Green Chem,2011,13:2285-2314
13 Pennacchio A,Giordano A,Pucci B,et al.Biochemical characterization of a recombinant short-chain NAD(H)-dependent dehydrogenase/reductase from Sulfolobus acidocaldarius.Extremophiles,2010,14:193-204
14 Kavanagh K L,J?rnvall H,Persson B,et al.Medium-and short-chain dehydrogenase/reductase gene and protein families.Cell Mol Life Sci,2008,65:3895-3906
15 Knoll M,Pleiss J.The Medium-chain dehydrogenase/reductase engineering database:A systematic analysis of a diverse protein family to understand sequence-structure-function relationship.Protein Sci,2008,17:1689-1697
16 Hyndman D,Bauman D R,Heredia V V,et al.The aldo-keto reductase superfamily homepage.Chemico-Biol Interact,2003,143-144:621-631
17 Jez J M,Bennett M J,Schlegel B P,et al.Comparative anatomy of the aldo-keto reductase superfamily.Biochem J,1997,326:625-636
18 Couture J F,Legrand P,Cantin L,et al.Loop relaxation,a mechanism that explains the reduced specificity of rabbit 20α-hydroxysteroid dehydrogenase,a member of the aldo-keto reductase superfamily.J Mol Biol,2004,339:89-102
19 Kizaki N,Yasohara Y,Nagashima N,et al.Characterization of novel alcohol dehydrogenase of Devosia riboflavina involved in stereoselective reduction of 3-pyrrolidinone derivatives.J Mol Catal B-Enzym,2008,51:73-80
20 Yamada-Onodera K,Kojima K,Takase Y,et al.Cloning,sequence analysis,and expression in Escherichia coli of gene encoding N-benzyl-3-pyrrolidinol dehydrogenase from Geotrichum capitatum.J Biosci Bioeng,2007,104:379-384
21 Liang J,Lalonde J,Borup B,et al.Development of a biocatalytic process as an alternative to the(-)-DIP-Cl-mediated asymmetric reduction of a key intermediate of montelukast.Org Proc Res Dev,2009,14:193-198
22 Nie Y,Wang S,Xu Y,et al.Enzyme engineering based on X-ray structures and kinetic profiling of substrate libraries:alcohol dehydrogenases for stereospecific synthesis of a broad range of chiral alcohols.ACS Catal,2018,8:5145-5152
23 Lavandera I,Kern A,Ferreira-Silva B,et al.Stereoselective bioreduction of bulky-bulky ketones by a novel ADH from Ralstonia sp..J Org Chem,2008,73:6003-6005
24 Athanasiou N,Smallridge A J,Trewhella M A.Baker’s yeast mediated reduction ofβ-keto esters andβ-keto amides in an organic solvent system.J Mol Catal B-Enzym,2001,11:893-896
25 Hummel W.New alcohol dehydrogenases for the synthesis of chiral compounds.New Enzym Org Syn,1997,58:145-184
26 Naik H G,Yeniad B,Koning C E,et al.Investigation of asymmetric alcohol dehydrogenase(ADH)reduction of acetophenone derivatives:Effect of charge density.Org Biomol Chem,2012,10:4961-4967
27 Zhu D,Hua L.Enantioselective enzymatic reductions of sterically bulky aryl alkyl ketones catalyzed by a NADPH-dependent carbonyl reductase.J Org Chem,2006,71:9484-9486
28 K?dziora K,Díaz-Rodríguez A,Lavandera I,et al.Laccase/TEMPO-mediated system for the thermodynamically disfavored oxidation of 2,2-dihalo-1-phenylethanol derivatives.Green Chem,2014,16:2448-2453
29 Ishihara K,Kato C,Yamaguchi H,et al.Stereoselective reduction of carbonyl compounds with actinomycete:purification and characterization of threeα-keto ester reductases from Streptomyces avermitilis.Biosci Biotech Biochem,2008,72:3249-3257
30 Yamaguchi H,Nakajima N,Ishihara K.Purification and characterization of twoα-keto ester reductases from Streptomyces thermocyaneoviolaceus IFO 14271.Biosci Biotech Biochem,2002,66:588-597
31 Yadav G D,Sajgure A D,Dhoot S B.Insight into microwave irradiation and enzyme catalysis in enantioselective resolution of RS-(±)-methyl mandelate.J Chem Technol Biotechnol,2008,83:1145-1153
32 Guo J L,Mu X Q,Xu Y.Integration of newly isolated biocatalyst and resin-based in situ product removal technique for the asymmetric synthesis of(R)-methyl mandelate.Bioprocess Biosyst Eng,2010,33:797-804
33 Kasprzak J,Rauter M,Denter S,et al.Synthesis of ethyl(R)-mandelate using recombinant carboxydothermus hydrogenoformans alcohol dehydrogenase produced by two yeast species.J Mol Catal B-Enzym,2016,133:176-186
34 Milagre H M S,Milagre C D F,Moran P J S,et al.Reduction of ethyl benzoylformate mediated by Saccharomyces cerevisiae entrapped in alginate fibers with double gel layers in a continuously operated reactor.Enzyme Microbial Tech,2005,37:121-125
35 Nikaido T,Matsuyama A,Ito M,et al.Stereospecific reduction of 2-oxo-4-phenylbutanoate to(R)-2-hydroxy-4-phenylbutanoate with microbial cells.Biosci Biotech Biochem,2014,56:2066-2067
36 de Lacerda P S B,Ribeiro J B,Leite S G F,et al.Microbial reduction of ethyl 2-oxo-4-phenylbutyrate.Searching for R-enantioselectivity.New access to the enalapril like ACE inhibitors.Tetrahedron-Asymmetry,2006,17:1186-1188
37 Ni Y,Li C X,Ma H M,et al.Biocatalytic properties of a recombinant aldo-keto reductase with broad substrate spectrum and excellent stereoselectivity.Appl Microbiol Biotechnol,2010,89:1111-1118
38 Oda S,Inada Y,Kobayashi A,et al.Production of ethyl(R)-2-hydroxy-4-phenylbutanoate via reduction of ethyl 2-oxo-4-phenylbutanoate in an interface bioreactor.Biosci Biotech Biochem,2014,62:1762-1767
39 Lacerda P S B,Ribeiro J B,Leite S G F,et al.Microbial enantioselective reduction of ethyl-2-oxo-4-phenyl-butanoate.Biochem Eng J,2006,28:299-302
40 Zhang W,Ni Y,Sun Z,et al.Biocatalytic synthesis of ethyl(R)-2-hydroxy-4-phenylbutyrate with Candida krusei SW2026:A practical process for high enantiopurity and product titer.Process Biochem,2026,44:1270-1275
41 Ou Z,Chen X,Ying G,et al.Continuous preparation of(S)-3-hydroxy-3-phenylpropionate by asymmetric reduction of 3-oxo-3-phenylpropionic acid ethyl ester with Saccharomyces cerevisiae CGMCC No.2266 in a membrane reactor.Biotechnol Bioproc E,2011,16:320-326
42 Wang P Y,Tsai S W.Hydrolytic resolution of(R,S)-3-hydroxy-3-phenylpropionates by esterase from Klebsiella oxytoca:Effects of leaving alcohol,covalent immobilization and aqueous pH.J Mol Catal B-Enzymatic,2009,59:70-75
43 Engelking H,Pfaller R,Wich G,et al.Reaction engineering studies onβ-ketoester reductions with whole cells of recombinant Saccharomyces cerevisiae.Enzyme Microbial Tech,2006,38:536-544
44 Chen J,Yan M,Xu L.Efficient synthesis of(S)-N-Boc-3-hydroxypiperidine using an(R)-specific carbonyl reductase from Candida parapsilosis.World J Microbiol Biotechnol,2017,33:61-72
45 Yamada-Onodera K,Fukui M,Tani Y.Purification and characterization of alcohol dehydrogenase reducing N-benzyl-3-pyrrolidinone from Geotrichum capitatum.J Biosci Bioeng,2007,103:174-178
46 Liu H,Hoff B H,Anthonsen T.Chemo-enzymatic synthesis of the antidepressant duloxetine and its enantiomer.Chirality,2000,12:26-29
47 Soni P,Banerjee U C.Biotransformations for the production of the chiral drug(S)-duloxetine catalyzed by a novel isolate of Candida tropicalis.Appl Microbiol Biotechnol,2005,67:771-777
48 Gong X M,Qin Z,Li F L,et al.Development of an engineered ketoreductase with simultaneously improved thermostability and activity for making a bulky atorvastatin precursor.ACS Catal,2019,9:147-153
49 Liu Z Q,Wu L,Zhang X J,et al.Directed evolution of carbonyl reductase from Rhodosporidium toruloides and its application in stereoselective synthesis of tert-butyl(3R,5S)-6-chloro-3,5-dihydroxyhexanoate.J Agric Food Chem,2017,65:3721-3729
50 Xu G C,Shang Y P,Yu H L,et al.Identification of key residues in Debaryomyces hansenii carbonyl reductase for highly productive preparation of(S)-aryl halohydrins.Chem Commun,2015,51:15728-15731
51 Huang L,Ma H M,Yu H L,et al.Altering the substrate specificity of reductase Cg KR1 from Candida glabrata by protein engineering for bioreduction of aromaticα-keto esters.Adv Synth Catal,2014,356:1943-1948
52 Zheng G W,Liu Y Y,Chen Q,et al.Preparation of structurally diverse chiral alcohols by engineering ketoreductase Cg KR1.ACS Catal,2017,7:7174-7181
53 Li A,Ye L,Yang X,et al.Reconstruction of the catalytic pocket and enzyme-substrate interactions to enhance the catalytic efficiency of a shortchain dehydrogenase/reductase.ChemCatChem,2016,8:3229-3233
54 Qu G,Zhang K,Jiang Y,et al.The Nobel Prize in Chemistry 2018:the directed evolution of enzyme and the phage display technologies(in Chinese).J Biol,2019,36:1-6,19[曲戈,张锟,蒋迎迎,等.2018诺贝尔化学奖:酶定向进化与噬菌体展示技术.生物学杂志,2019,36:1-6,19]
55 Parkot J,Gr?ger H,Hummel W.Purification,cloning,and overexpression of an alcohol dehydrogenase from Nocardia globerula reducing aliphatic ketones and bulky ketoesters.Appl Microbiol Biotechnol,2010,86:1813-1820
56 Liang C,Nie Y,Mu X,et al.Gene mining-based identification of aldo-keto reductases for highly stereoselective reduction of bulky ketones.Bioresour Bioprocess,2018,5:33
57 Li R,Wijma H J,Song L,et al.Computational redesign of enzymes for regio-and enantioselective hydroamination.Nat Chem Biol,2018,14:664-670