Molecular mechanism of substrate oxidation in lytic polysaccharide monooxygenases: Insight from Theoretical Investigations

Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes that today comprise a large enzyme superfamily, grouped into the distinct members AA9–AA17 (with AA12 exempted). The LMPOs have the potential to facilitate the up-cycling of biomass waste products by boosting the breakdown of cellulose and other recalcitrant polysaccharides. The cellulose bio-polymer is the main component of biomass waste and comprises thus a large, unexploited resource. The LMPOs work through a catalytic, oxidative reaction whose mechanism is still controversial. For instance, the nature of the intermediate performing the oxidative reaction is an open question, and the same holds for the employed co-substrate. We here review theoretical investigations addressing these questions. The applied theoretical methods are usually based on quantum mechanics (QM), often combined with molecular mechanics (QM/MM). We discuss advantages and disadvantages of the employed theoretical methods and comment on the interplay between theoretical and experimental results.