Targeting the reactive intermediate in polysaccharide monooxygenases

Erik D Hedegård,Ulf Ryde

doi:10.1007/s00775-017-1480-1

Abstract

Lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes that can enhance polysaccharide depolymerization through an oxidative mechanism, making them interesting for the production of biofuel from cellulose. However, the details of this activation are unknown; in particular, the nature of the intermediate that attacks the glycoside C–H bond in the polysaccharide is not known, and a number of different species have been suggested. The homolytic bond-dissociation energy (BDE) has often been used as a descriptor for the bond-activation power, especially for inorganic model complexes. We have employed quantum-chemical cluster calculations to estimate the BDE for a number of possible LPMO intermediates to bridge the gap between model complexes and the actual LPMO active site. The calculated BDEs suggest that the reactive intermediate is either a Cu(II)–oxyl, a Cu(III)–oxyl, or a Cu(III)–hydroxide, which indicate that O–O bond breaking occurs before the C–H activation step.

Highlights

The class of enzymes called lytic polysaccharide monooxygenases (LPMOs) [1,2,3,4,5,6,7,8,9,10] has recently attracted considerable attention due to their ability to enhance polysaccharide depolymerization, thereby providing a route to efficient conversion of polysaccharides into smaller sugars [11,12,13,14,15,16]
It can be seen that for the [Cu–OOH]2+ species, the bond-dissociation energy (BDE) is rather low, 317 kJ/ mol, compared to 423–434 kJ/mol for the saccharide substrate, which excludes this species as a putative reactive intermediate for C–H activation in LPMO
The same applies to the [Cu–OO]+ intermediate, for which the BDE is 301 kJ/mol

Summary

Introduction

The class of enzymes called lytic polysaccharide monooxygenases (LPMOs) [1,2,3,4,5,6,7,8,9,10] has recently attracted considerable attention due to their ability to enhance polysaccharide depolymerization, thereby providing a route to efficient conversion of polysaccharides into smaller sugars [11,12,13,14,15,16]. The enhancement proceeds by an oxidative mechanism in which the otherwise unreactive C–H bonds in the linkage between the sugar units of the polysaccharides are activated. The equatorial ligand sphere consists of three nitrogen donor atoms in a so-called histidine brace moiety [1].

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Conclusion