Computational examination of the lytic polysaccharide monooxygenase reaction mechanism

Lytic polysaccharide monooxygenases (LPMOs) are a newly discovered enzymatic paradigm for the depolymerization of cellulose. LPMOs have been shown to cleave glycosidic linkages via tandem oxidation and hydrolysis of cellulose, but the detailed molecular mechanism was not at first apparent. We have recently employed density functional theory calculations to compare several hypothesized mechanisms for LPMO action on cellulose, which revealed that LPMOs likely employ a powerful copper-oxyl species for substrate hydroxylation and subsequent glycosidic bond cleavage. We also investigated the role of the N-terminal histidine methylation, which has been hypothesized to modify the reactivity of the enzyme. LPMOs are of emerging importance in industrial biomass depolymerization given their synergy with traditional hydrolytic enzymes, and this study suggests the molecular-level steps involved in their catalytic action.