Enzymatic C-H Oxidation by Tyrosyl Radicals

Johns Hopkins University, Baltimore MD

Investigators

Abstract

This award will support work by Professor Justine Roth at Johns Hopkins University to examine a plant-derived fatty acid alpha-dioxygenase which is believed to be a member of a family of enzymes that utilize tyrosyl radicals for catalysis. The ability of protein-derived radicals to mediate selective C-H oxidation using molecular oxygen has not been understood. The project features a mechanistic study that will allow the kinetics and thermodynamics of fatty acid oxidation to be characterized. Measurements of deuterium kinetic isotope effects as a function of temperature and substrate C-H bond strength will reveal the nature of the reaction barrier, which in this case also controls enzyme turnover. The results will be analyzed using Marcus Theory to elucidate the origins of enzyme catalysis. Insights of this kind are fundamentally important in the rational engineering of biological and chemical catalysts as well as the applications of enzymes in the industrial production of commodity chemicals. A broader objective of this research is to expose students to the importance of oxidative phenomena in chemistry and biology. An educational enrichment program for Baltimore City high school students has been initiated in collaboration with the Teach for America Baltimore Corps. This program will expose students to higher education in the biological and physical sciences, specifically at Johns Hopkins University. The program will also cultivate opportunities for summer internships and research experiences within the P.I.'s laboratories.