NIE Yao&XU Yan et al.ACS Catal., 2018, 8 (6), pp 5145–5152
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.
The narrow substrate scope of naturally occurring alcohol dehydrogenases (ADHs) greatly limits the enzymatic synthesis of important chiral alcohols. On the basis of X-ray crystal structures and kinetic profiling of a substrate library, we engineered variants of the stereospecific alcohol dehydrogenase from Candida parapsilopsis. This resulted in a set of four mutant enzymes which enable the asymmetric reduction of a broad range of prochiral ketones, including valuable pharmaceuticals and fine chemicals. The engineering strategy of this study paves the way for creating additional ADHs tailored for production of complex chiral alcohols.