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Substituent Position‐Controlled Stereoselectivity in Enzymatic Reduction of Diaryl‐ and Aryl(heteroaryl)methanones
Author(s) -
Li Zhining,
Wang Zexu,
Wang Yuhan,
Wu Xiaofan,
Lu Hong,
Huang Zedu,
Chen Fener
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201801543
Subject(s) - chemistry , stereoselectivity , substituent , aryl , steric effects , substrate (aquarium) , stereochemistry , stereospecificity , enantiomer , enantiomeric excess , combinatorial chemistry , enantioselective synthesis , organic chemistry , catalysis , alkyl , oceanography , geology
We report here the discovery of a novel ketoreductase (KRED), named KmCR2, with a broad substrate spectrum on bioreduction of sterically bulky diaryl‐ and aryl(heteroaryl)methanones. The position of the substituent on aromatic rings ( meta versus para or ortho ) was revealed to control the stereospecificity of KmCR2. The stereoselective preparation of both enantiomers of diaryl‐ or aryl(heteroaryl)methanols using strategically engineered substrates with a traceless directing group (bromo group) showcased the potential application of this substrate‐controlled bioreduction reaction. The combined use of substrate engineering and protein engineering, was demonstrated to be a useful strategy in efficiently improving stereoselectivity or switching stereopreference of enzymatic processes.