文献类型：期刊文献

英文题名：Enantioselective Synthesis of Chiral Vicinal Amino Alcohols Using Amine Dehydrogenases

作者：Chen, Fei-Fei[1,2];Cosgrove, Sebastian C.[2];Birmingham, William R.[2];Mangas-Sanchez, Juan[2];Citoler, Joan[2];Thompson, Matthew P.[2,3];Zheng, Gao-Wei[1];Xu, Jian-He[1];Turner, Nicholas J.[2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Univ Manchester, Sch Chem, Manchester Inst Biotechnol, 131 Princess St, Manchester M1 7DN, Lancs, England;[3]EnginZyme AB, Teknikringen 38A, S-11428 Stockholm, Sweden

年份：2019

卷号：9

期号：12

起止页码：11813

外文期刊名：ACS CATALYSIS

收录：;EI(收录号：20194807761100);WOS:【SCI-EXPANDED(收录号:WOS:000502169900118)】；

基金：The work was financially supported by the National Natural Science Foundation of China (Nos. 21472045, 21878085, 21536004, and 21871085). F.-F.C. gratefully acknowledges the China Scholarship Council for providing a scholarship to support his one year's overseas study in the UK. S.C.C. acknowledges the UK Catalysis Hub (EPSRC) for funding. W.RB., J.M.-S., and N.J.T. acknowledge an ERC Advanced Grant (Grant Number 742987). We are also grateful to Dr Reynard Spiess, Dr Fabio Parmeggiani, and Dr Kun Huang for their valuable assistance with MS, NMR, and HPLC analyses, respectively.

语种：英文

外文关键词：amine dehydrogenase; biocatalysis; chiral amino alcohols; directed evolution; reductive amination

摘要：Chiral vicinal amino alcohols are an important motif found in many biologically active molecules. In this study, biocatalytic reductive amination of alpha-hydroxy ketones with ammonia was investigated using engineered amine dehydrogenases (AmDHs) derived from the leucine amino acid dehydrogenase (AADH) from Lysinibacillus fusiformis. The AmDHs thus identified enabled the synthesis of (S)-configured vicinal amino alcohols from the corresponding alpha-hydroxy ketones in up to 99% conversions and >99% ee. One of the AmDH variants was used to prepare a key intermediate for the antituberculosis pharmaceutical ethambutol.