Enzymes to Enable a Biocatalytic Cascade for Small Molecule API

Enonereductases (EREDs) and ketoreductases (KREDs) are selective, sustainable alternatives to traditional asymmetric hydrogenation. We developed an ERED/KRED enzymatic cascade to install two stereocenters on a cyclohexyl ring in the synthesis of BMS-986278, a potent LPA1 antagonist. Protein engineering and process optimization led to major efficiency gains and a four-fold reduction in PMI compared to the original non-biocatalytic route. This innovation was recognized with the 2023 Peter J. Dunn Award for its significant green chemistry impact.