Deracemization of aryl secondary alcohols via enantioselective oxidation and stereoselective reduction with tandem whole-cell biocatalysts

Abstract

Deracemization of racemic 1-phenylethanol, i.e., stereoinversion of ( R)-1-phenylethanol to ( S)-1-phenylethanol, has been successfully realized via concurrent enantioselective oxidation and stereoselective reduction employing whole-cell biocatalysts of an alcohol dehydrogenase and a ketone reductase with opposite stereoselectivity in one-pot. One biocatalyst is Microbacterium oxydans ECU2010 which catalyzes stereoselective oxidation of ( R)-secondary alcohols to corresponding ketones and another is Rhodotorula sp. AS2.2241 which reduces the ketones to ( S)-secondary alcohols. Each of the whole-cell biocatalysts has its own in vivo cofactor regeneration system so that there is no need to add the expensive cofactor and/or the oxidoreductase for the cofactor regeneration. To explore the generality of this method, a broad range of racemic aryl secondary alcohols were efficiently deracemized to their ( S)-enantiomers by combination of the two microorganisms, affording optically pure secondary alcohols in high yields (86.5–99%) and excellent optical purity (>99% ee). Our method represents an easy going, cheap and environmentally benign way for the biocatalytic synthesis of chiral aryl secondary alcohols from their racemates.