Directed evolution of biocatalysts for asymmetric hydrogen atom transfer reactions

The National Institute of General Medical Sciences awarded the University of California, Los Angeles $420,981 on March 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to develop engineered enzymatic catalysts for asymmetric hydrogen atom transfer reactions in synthetic chemistry.

The research integrates organic chemistry, protein engineering, bioinorganic chemistry, and computational modeling to design and evolve biocatalysts that enable metal-hydride-mediated radical reactions with precise stereocontrol. The engineered catalysts will unlock stereoselective olefin functionalization for carbon-carbon bond-forming and reductive processes, with mechanistic studies revealing design principles for future biocatalysts. The work advances pharmaceutical synthesis and construction of complex molecules relevant to human health.

Performance occurs in Los Angeles, California through the University's Office of Research Administration. The period of performance runs from March 1, 2026, through February 28, 2031. This is a project grant, a standard assistance type under NIGMS's portfolio of investigator-initiated biomedical research supporting basic science that advances disease diagnosis, treatment, and prevention.

Abstract

The rise of biocatalysis is transforming synthetic chemistry by enabling highly selective and sustainable transformations. Despite advances, achieving precise stereocontrol in radical-mediated reactions remains a significant frontier. This interdisciplinary research program integrates expertise in organic chemistry, protein engineering, bioinorganic chemistry, and computational modeling to design and evolve enzymatic catalysts for metal-hydride-mediated radical reactions-a versatile yet historically challenging class of asymmetric transformations with broad synthetic utility. These engineered biocatalysts will unlock stereoselective olefin functionalization, enabling diverse carbon-carbon bond-forming and reductive processes without precedent in natural biochemistry. Mechanistic studies will reveal the principles behind these new enzymatic functions, enabling rational design of future biocatalysts. These biocatalysts will advance pharmaceutical synthesis and the construction of complex molecules important to human health.