Enzymatic enantioselective reduction of α-ketoesters by a thermostable 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis

Abstract

A thermostable 7α-hydroxysteroid dehydrogenase (7-HSDH) from Bacteroides fragilis ATCC 25285 was cloned and over-expressed in E. coli, and its substrate specificity and stereoselectivity toward reduction of various ketones were examined. This alcohol dehydrogenase was active toward a series of aromatic and bulky aliphatic α-ketoesters. The substituents at the phenyl ring of aromatic α-ketoesters greatly affected the activity, but their effects on enantioselectivity were minimal. The synthetic application of this enzyme was then demonstrated through the preparation of a few α-hydroxy carboxylic acid esters of pharmaceutical interest.