Federal Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded Princeton University $165,366 under the Biomedical Research and Research Training program (CFDA 93.859) effective May 1, 2026, through April 30, 2031. This Project Grant supports the development of photoenzymes—biological catalysts that leverage photonic energy to drive chemical reactions—for selective chemical synthesis applications. The research addresses critical challenges in organic radical chemistry by engineering naturally occurring dark enzymes to function as photoenzymes, enabling enhanced control over enantio-, regio-, and chemoselectivity in radical-based reactions that would be difficult to achieve using conventional synthetic methods.

The project delivers multiple lines of research innovation, including: (1) merging ene-reductase catalyzed hydroalkylations with imine reductases to synthesize saturated heterocycles with multiple stereocenters and precise stereochemical control; (2) developing regioselective difluoro- and trifluoromethylation strategies for arenes to access substitution patterns unavailable through existing C-H functionalization approaches; (3) utilizing Baeyer-Villager monooxygenases as photoreductants for styrenyl alkene-to-benzylic radical conversions enabling N-heterocyclic synthesis; and (4) engineering new radical initiation mechanisms, including lactate monooxygenase modifications for asymmetric CSP3-CSP3 cross-coupling reactions. Research will be conducted at Princeton University's facility in Princeton, New Jersey.