Expanding the catalytic landscape of metalloenzymes with lytic polysaccharide monooxygenases

Lytic polysaccharide monooxygenases (LPMOs) have an essential role in global carbon cycle, industrial biomass processing and microbial pathogenicity by catalysing the oxidative cleavage of recalcitrant polysaccharides. Despite initially being considered monooxygenases, experimental and theoretical studies show that LPMOs are essentially peroxygenases, using a single copper ion and H2O2 for C-H bond oxygenation. Here, we examine LPMO catalysis, emphasizing key studies that have shaped our comprehension of their function, and address side and competing reactions that have partially obscured our understanding. Then, we compare this novel copper-peroxygenase reaction with reactions catalysed by haem iron enzymes, highlighting the different chemistries at play. We conclude by addressing some open questions surrounding LPMO catalysis, including the importance of peroxygenase and monooxygenase reactions in biological contexts, how LPMOs modulate copper site reactivity and potential protective mechanisms against oxidative damage. Lytic polysaccharide monooxygenases are key enzymes in biomass processing and pathogenicity. They are, to our knowledge, the first known copper enzymes capable of utilizing H2O2 to hydroxylate C-H bonds. This Review draws a portrait of the catalytic paths at play and highlights outstanding questions in their reactivity.