CCVC: Lionel Cheruzel - Light-driven P450 biocatalysts featuring Ru(II)-polypyridyl complexes

Abstract:

The Cytochromes P450 are heme-thiolate enzymes that carry out selective oxyfunctionalization of a wide range of substrates C-H bonds using molecular dioxygen and two reducing equivalents. Recent efforts have focused on the use of light-harvesting units to trigger P450 activity upon visible light excitation. Our laboratory has taken advantage of Ru(II)-diimine complexes and their unique excited properties to harness the P450 synthetic potential. The covalent attachment of these photosensitizers to non-native single cysteine residues has enabled rapid electron injections into the heme domain of several bacterial P450 enzymes leading to high photocatalytic activity and coupling efficiency. The crystal structure of the most efficient hybrid enzyme reveals that the photosensitizer is ideally positioned to deliver electrons to the heme active site utilizing the natural electron transfer pathway. A combination of rational and directed evolution approaches are currently employed to optimize the biocatalyst photocatalytic activity and expand the scope of the light-driven P450 activity. In addition, we recently sought to capitalize on the photoredox properties of these inorganic complexes combined with the P450 biocatalysis to develop novel chemoenzymatic approaches including selective light-driven trifluoromethylation/ oxyfunctionalization of several substituted arenes.

Bio:

Dr. Lionel Cheruzel grew up in Cannes, South of France, before moving to the United States in 1999 to pursue his graduate studies. Upon completion of his Ph.D. at the University of Louisville, KY, he joined as a postdoctoral fellow the laboratory of Prof. Harry B. Gray at the California Institute of Technology in Pasadena, CA. In Fall 2009, he started as an assistant professor in the Department of Chemistry at San Jose State University. He was promoted to full professor in August 2019. He is the recipient of the 2013 Journal of Biological Chemistry/Herbert Tabor Young Investigator Award and the 2019 Henry Dreyfus Teacher Scholar Award.