Mechanism of fungal polysaccharide monooxygenases

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Michael Marletta from The Scripps Research Institute to investigate the recently discovered polysaccharide monooxygenases (PMOs), enzymes that catalyze the degradation of cellulose. Cellulose is the major constituent of biomass in nature. Despite years of study, the efficient and economical degradation of cellulose remains a limiting factor in the industrial production of biofuels from cellulose. PMOs could help to overcome the prohibitive costs associated with cellulose degradation. PMOs use a copper active site to oxidize specific positions on cellulose. This project will investigate the chemistry by which these enzymes break the cellulose backbone and the determinants of regioselective (i.e. specific site) oxidation. The research contributes to the current quest for green and sustainable energy, creates opportunities for the education of future scientists capable of work in the field of bioenergy, and raises the awareness of college and high school students of STEM careers. The objective of this project is to gain insight into the mechanism by which the newly discovered oxygen- and copper-dependent fungal PMOs catalyze the regioselective hydroxylation and oxidation of glycosidic bonds of crystalline cellulose. The research will focus on the direct identification and characterization of the copper-based species in the catalytic cycle. The kinetics of interconversion of these species, the electron transfer during catalysis, the role of the conserved active site hydrogen bonding network, and the factors governing the regioselectivity of the reactions catalyzed by PMO will be studied using site directed mutagenesis, rapid kinetic techniques, spectroscopic methods and biochemical assays. The proposed studies will contribute fundamental knowledge to the metal-catalyzed oxygen activation chemistry and to the development of alternative fuels.