Improved enantioselectivity of BioH in kinetic resolution of methyl ()-3-cyclohexene-1-carboxylate by combinatorial modulation of steric and aromatic interactions.

As a chiral precursor for the important anticoagulant Edoxaban, enantioselective synthesis of ()-3-cyclohexene-1-carboxylic acid is of great significance. The complicated procedures and generation of massive solid waste discourage its chemical synthesis, and the alternative biocatalysis route calls for an enzyme capable of asymmetric hydrolysis of racemic methyl-3-cyclohexene-1-carboxylate. To this end, we engineered the esterase BioH for improved -enantioselectivity via rational design.