CAREER: Mechanism of Cytochrome P450 Alkene Biosynthesis

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CAREER: Mechanism of Cytochrome P450 Alkene BiosynthesisWith this CAREER award, the Chemistry of Life Processes in the Chemistry Division of NSF is funding Dr. Thomas Makris from the University of South Carolina to study the mechanism of OleT, a recently discovered enzyme that is involved in the synthesis of hydrocarbons. The biocatalytic production of hydrocarbons provides a potential route to sustainably produce fuels that are compatible within the existing energy infrastructure. The atypical reaction catalyzed by OleT consumes hydrogen peroxide, a toxic reactive oxygen species, and transforms biologically abundant fatty acids into alkenes without any additional input of energy. The goal of this research is to understand both the chemistry of this reaction, and the molecular details which promote it. Additional broader impacts of this research are in its active involvement of undergraduate and high school students, and the community at large, in an ongoing protein engineering initiative that introduces this hydrocarbon producing capacity into a related enzyme. The award also supports research for undergraduates from the home institution, and abroad, through a collaborative exchange with a liberal arts college for women, and provides the first research opportunities to high-school students from underrepresented minorities.The cytochromes P450 are a ubiquitously expressed superfamily of thiolate-ligated heme enzymes that catalyze a diverse set of physiologically important chemical reactions. Cytochrome P450 enzymes typically insert oxygen atoms into organic substrates using a ferryl intermediate known as Compound I. OleT forms Compound I, but instead catalyzes a fundamentally different reaction that does not involve oxygen insertion. The origins for this unusual metal-oxo reprogramming are being probed by biochemical, kinetics, spectroscopic and structural methods. These methodologies evaluate the individual contributions of electronic structure, secondary coordination sphere, and substrate positioning on promoting the carbon-carbon scission reaction. Dr. Makris has devised an innovative educational plan, termed Fats to Fuels, that is well integrated into the proposed studies of OleT. In this plan, undergraduate students and the local community are engaged in learning how fats can be converted to hydrocarbon fuel sources. This research has the potential to impact society with respect to developing new hydrocarbon sources as alternatives to fossil fuels.