The stereoselective synthesis of chiral pyrrolidine motifs is essential to vibegron production but remains challenging using conventional chemical routes. Here we report an imine reductase (IRED) catalyzed asymmetric imine reduction to access a key vibegron intermediate. Directed evolution afforded a highly efficient variant delivering 94% conversion and >99% d.e. Combined enzyme and host engineering enabled clean whole cell catalysis, establishing a robust and scalable biocatalytic platform.
Bao et al. (Mon,) studied this question.