Lytic Polysaccharide Monooxygenase

Abstract

Abstract For decades, the enzymatic conversion of recalcitrant polysaccharides such as cellulose and chitin was thought to rely on the synergistic action of hydrolytic enzymes, but recent work has shown that lytic polysaccharide monooxygenases (LPMOs) are important contributors to this process. LPMOs that are divided into three auxiliary activities (AA) families share a structural fold, but there is no detectable sequence identity between members of different families. The general core structure of LPMOs is an immunoglobulin‐like distorted β‐sandwich fold, consisting of antiparallel β‐strands connected by loops with a varying number of α‐helix insertions. LPMOs have a flat binding surface that harbors a type‐2 copper center that is coordinated by three nitrogens with a T‐shaped geometry that has been referred to as the histidine brace. Two of the nitrogens come from the imidazole side chain and the main chain amino group of the N‐terminal histidine, whereas the third nitrogen is from a second conserved histidine. The role of the copper ion is to reduce dioxygen, which requires electrons from an external electron donor. The reduced dioxygen likely abstracts a hydrogen from the substrate, which eventually leads to cleavage of the β‐1,4 glycosidic linkage. While copper‐dependent enzymes usually use more than one metal to activate O 2 by multielectron reduction, LPMOs use only a single Cu center for catalysis. Central for LPMO activity is a flat protein surface with a few conserved residues suggesting a role in substrate binding and the T‐shape of the copper site that permits strong O 2 binding with very little reorganization energy allowing the thermodynamically difficult one‐electron reduction activating the oxygen.