Fungal cellulose degradation by oxidative enzymes: from dysfunctional GH61 family to powerful lytic polysaccharide monooxygenase family

Abstract

Our understanding of fungal cellulose degradation has shifted dramatically in the past few years with the characterization of a new class of secreted enzymes, the lytic polysaccharide monooxygenases (LPMO). After a period of intense research covering structural, biochemical, theoretical and evolutionary aspects, we have a picture of them as wedge-like copper-dependent metalloenzymes that on reduction generate a radical copper-oxyl species, which cleaves mainly crystalline cellulose. The main biological function lies in the synergism of fungal LPMOs with canonical hydrolytic cellulases in achieving efficient cellulose degradation. Their important role in cellulose degradation is highlighted by the wide distribution and often numerous occurrences in the genomes of almost all plant cell-wall degrading fungi. In this review, we provide an overview of the latest achievements in LPMO research and consider the open questions and challenges that undoubtedly will continue to stimulate interest in this new and exciting group of enzymes.

Keywords: AA9; GH61; cellobiose dehydrogenase; oxidative cellulose degradation.

Figure 1:

Representative AA9 LPMO from N. crassa selected for lowest average RMSD value among Protein Data Bank models. The structure shown is Q7SA19 [47], and the highlighted loops and residues also incorporate information from [10]. Highlighted in yellow, blue and red are the loops L2, the C-terminal and the short loop, respectively. The copper atom is shown as a sphere with the coordinating residues (two histidines) and the axial tyrosine in stick representation. The three tyrosines of loops L2 and the C-terminal loop, presumed to interact with cellulose substrate, are also indicated in stick representation. The image was created using PDB entry 4EIS with the UCSF Chimera package developed by the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco [48]. (A colour version of this figure is available online at: http://bfg.oxfordjournals.org)

Figure 2:

The histidine brace in N. crassa Q7SA19 (PDB ID: 4EIS). Six amino-acids surrounding the metal-binding site are shown in stick representation. Copper is shown as a sphere. Octahedral copper coordination is indicated by dashed lines. The solvent exposed axial ligand is modeled as a hydrogen peroxide (stick) and the fourth equatorial ligand is water (sphere).

Figure 3:

Proposed reactive oxygen species generated by LPMO enzymes. The arrows indicate the sites of attack on cellulose observed for different LPMOs.