Substituent Position‐Controlled Stereoselectivity in Enzymatic Reduction of Diaryl‐ and Aryl(heteroaryl)methanones

Abstract 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. magnified image