Cascade Biotransformations for Enantioconvergent Conversion of Racemic Styrene Oxides to (R)-Mandelic Acids

Abstract

Enantioconvergent conversions of rac-styrene oxides to (R)-mandelic acids were achieved by an enzymatic cascade comprising enantioconvergent epoxide hydrolysis, (R)-enantioselective alcohol oxidation, and aldehyde oxidation. The concept was proven using a cocktail of epoxide hydrolase (StEH) from S. tuberosum, mutant alditol oxidase (Aldo(M)) from S. coelicolor, and phenylacetaldehyde dehydrogenase (EcALDH) from E. coli. Practical application was demonstrated using cells of single E. coli strain or coupled E. coli strains expressing the necessary enzymes, producing (R)-mandelic acid in up to 175 mM (>99% ee, 88%–92% yields). (R)-4-Fluoro-, (R)-4-chloro-, and (R)-4-bromo-mandelic acid were produced in >99% ee with 87%, 76%, and 45% yields, respectively.