A “Second-Generation Process” for the Synthesis of l-Neopentylglycine:  Asymmetric Reductive Amination Using a Recombinant Whole Cell Catalyst

Abstract

A “second-generation process” for the enantioselective synthesis of l-neopentylglycine has been developed, realizing the first whole cell-catalyzed approach to this pharmaceutically interesting, bulky amino acid. The synthesis of this nonnatural amino acid proceeds highly efficiently via a reductive amination of the corresponding α-keto acid in the presence of a recombinant whole cell catalyst, bearing a leucine dehydrogenase and formate dehydrogenase. The desired l-neopentylglycine was obtained with >95% conversion and a high enantioselectivity of >99% ee at substrate concentrations of up to 88 g/L.