Carboxylic acid reductases enable intramolecular lactamization reactions

Abstract

As a versatile type of enzyme, carboxylic acid reductases (CAR) can not only reduce various carboxylic acids to aldehydes in cooperation with cofactors ATP and NADPH but also catalyze the synthesis of amides and esters in the absence of NADPH. Here, we report an intramolecular cyclization catalyzed by CAR only with the use of ATP to transform amino acids into diverse lactams, including γ-/δ-/ε-lactams and chiral derivatives thereof. The observed wide substrate scope and selectivity enable potential applications to be implemented. Our results demonstrate that CAR-catalyzed lactamization is a promising approach for the synthesis of chiral lactam compounds under mild conditions, thereby enriching the toolbox for the biosynthesis of lactams as a viable alternative to purely chemical procedures.