Evaluation of substituent effects on activity and enantioselectivity in the enzymatic reduction of aryl ketones

Abstract

The enzymatic reduction of a series of substituted aryl ketones catalyzed by 24 isolated recombinant ketoreductases was studied and the substituent effects on activity and enantioselectivity were evaluated. When comparing p- and m-substituted acetophenones, the substituent significantly affects the activity of some of the tested ketoreductases, while it has little effect on the activity of other ketoreductases. Most of the tested ketoreductases were highly enantioselective in the reduction of these aryl ketones. The electronic properties, steric factors, and the ability to form a hydrogen bond to the substituents at the ortho-position play a significant role in determining both the activity and enantioselectivity of the ketoreductase-catalyzed reductions. From an applicability point of view, both enantiomers of the product aryl alcohols could be prepared via reduction catalyzed by one or more of the ketoreductases in most cases.