Semi-Rational Engineering a Carbonyl Reductase for the Enantioselective Reduction of beta-Amino Ketones
文献类型：期刊论文
| 作者 | Zhang, Dalong1,2; Chen, Xi1,2; Chi, Jing1,2,3; Feng, Jinhui1,2; Wu, Qiaqing1,2; Zhu, Dunming1,2 |
| 刊名 | ACS CATALYSIS
 |
| 出版日期 | 2015-04-01 |
| 卷号 | 5期号:4页码:2452-2457 |
| 关键词 | chiral gamma-amino alcohols beta-amino ketones enzyme engineering carbonyl reductase enantioselective reduction |
| 英文摘要 | Chiral 3-(dimethylamino)-1-phenylpropan-1-ol (2a) and 3-(dimethylamino)-1-(2-thienyl)-1-ol (2b) are very important intermediates for the synthesis of antidepressants. The mutant M242F/Q245T of a carbonyl reductase (SSCR) from Sporobolomyces salmonicolor AKU4429 catalyzed the reduction of 3-(dimethylamino)-1-phenylpropan-1-one (la) to the (S)-2a (28% ee). The combinatorial active-site saturation of this enzyme resulted in two mutants P170R/L174Y and P170H/L174Y, which catalyzed the reduction of la and 3-(dimethylamino)-1-(2-thienyl)-propan-1-one (1b) to give the (R)-gamma-amino alcohols with up to 95% ee, respectively. The individual site saturation mutagenesis of Pro170 and Leu174 revealed that Pro170 did not significantly affect the enzyme enantioselectivity toward la and 1b, whereas residue Leu174 played a critical role in determining the enantioselectivity. Mutant L174W catalyzed the reduction of la to the (S)-gamma-amino alcohol with increased enantioselectivity from 28% ee to 96% ee, although mutant L174Y exhibited (R)-preference in 88% ee. For 1b, the (R)-alcohol was obtained with 95% ee by using variant L174Y as the catalyst, whereas L174W exhibited (S)-preference in 65% ee. The kinetic studies indicated that catalytic efficiencies (k(cat)/K-m) of these mutants were also improved. The enzyme substrate docking provided some insights into the structural basis for the reversal of enantioselectivity by the substitution of Leu174. |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 类目[WOS] | Chemistry, Physical |
| 研究领域[WOS] | Chemistry |
| 关键词[WOS] | SINGLE-POINT MUTATION ; ASYMMETRIC HYDROGENATION ; SPOROBOLOMYCES-SALMONICOLOR ; DIRECTED EVOLUTION ; SATURATION MUTAGENESIS ; SELECTIVE INHIBITOR ; EPOXIDE HYDROLASE ; SEROTONIN-UPTAKE ; OPTICAL ISOMERS ; SUBSTRATE SCOPE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000352464400050 |
| 源URL | [http://124.16.173.210/handle/834782/1454]  |
| 专题 | 天津工业生物技术研究所_生物催化与绿色化工 朱敦明_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Engn Lab Ind Enzymes, Tianjin 300308, Peoples R China 2.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin Engn Ctr Biocatalyt Technol, Tianjin 300308, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Dalong,Chen, Xi,Chi, Jing,et al. Semi-Rational Engineering a Carbonyl Reductase for the Enantioselective Reduction of beta-Amino Ketones[J]. ACS CATALYSIS,2015,5(4):2452-2457. |
| APA | Zhang, Dalong,Chen, Xi,Chi, Jing,Feng, Jinhui,Wu, Qiaqing,&Zhu, Dunming.(2015).Semi-Rational Engineering a Carbonyl Reductase for the Enantioselective Reduction of beta-Amino Ketones.ACS CATALYSIS,5(4),2452-2457. |
| MLA | Zhang, Dalong,et al."Semi-Rational Engineering a Carbonyl Reductase for the Enantioselective Reduction of beta-Amino Ketones".ACS CATALYSIS 5.4(2015):2452-2457. |
入库方式： OAI收割
来源：天津工业生物技术研究所
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