Bioreduction of methyl o-chlorobenzoylformate at 500 g L~(-1) without external cofactors for efficient production of enantiopure clopidogrel intermediate

摘要

Biocatalytic reduction of methyl o-chlorobenzoylformate (CBFM) provides a green and direct access to methyl (R)-o-chloromandelate [(R)-CMM], an intermediate for a platelet aggregation inhibitor named clopidogrel. As much as 500 g L~(-1) of CBFM was stoichiometrically converted into enantiopure (R)-CMM at 20 °C by using a whole-cell catalyst coexpressing an aldo-keto reductase from Bacillus sp. and a glucose dehydrogenase (GDH). In addition to the high productivity of 812 g L~(-1) d~(-1), this new whole-cell reduction is attractive by eliminating the need of an added external cofactor.