Work

The C-terminal intrinsically disordered region of a fungal lytic polysaccharide monooxygenase binds copper and displays anti-fungal properties

Year: 2026

Type: article

Abstract: Lytic Polysaccharide Monooxygenases (LPMOs) are enzymes that play a crucial role in the degradation of complex polysaccharides such as cellulose and chitin. While LPMOs have attracted significant interest for industrial applications to convert biomass into biofuels, emerging evidence suggests alternative functions in fungal plant pathogenesis, microbial diseases and (micro)organism development. The AA14 LPMO family is widely distributed in filamentous fungi but remains enigmatic as its initially-suspected substrate specificity was recently challenged. In this study, we investigated the disordered C-terminal regions (dCTRs), found in more than half of AA14 family members and hypothesized to have functional relevance. Focusing on the Pycnoporus coccineus AA14A LPMO, we used small angle X-ray scattering (SAXS) and circular dichroism to show that its dCTR is highly disordered. It consists of a heavily glycosylated low complexity region followed by a charged C-terminal tail. We uncovered that the Pco AA14A dCTR binds copper ions through histidine residues located in the C-terminal tail. Using electron paramagnetic resonance (EPR), we further demonstrated that dimer formation occurs through an oxidative process involving copper and a redox-sensitive cysteine. Noting similarities between the last residues of the C-terminal tail and antimicrobial peptides, we investigated its potential antimicrobial function. We found that the positively charged region of the C-terminal tail selectively inhibits the growth of basidiomycete fungal spores. These data reveal that the dCTRs appended to AA14 LPMOs are functional regions that must be considered to unveil the role of these atypical LPMOs. Significance Statement Lytic polysaccharide monooxygenases (LPMOs) degrade complex polysaccharides and are central to biomass conversion. Their biological relevance is expanding, with emerging roles in fungal development and host interactions. Despite this broad potential, research has largely focused on their catalytic domain. One area that remains poorly understood is the function of their C-terminal region, predicted to be intrinsically disordered (dCTR). The AA14 LPMO family, whose substrate specificity remains enigmatic, is enriched in dCTRs. This study provides the first experimental evidence of the disordered nature of the dCTR of an AA14 LPMO. Using multidisciplinary approaches, we demonstrate that the dCTR binds metals and exhibits antifungal activity. These findings establish dCTRs as functional regions, essential for understanding the biological roles of LPMOs.

Source: International Journal of Biological Macromolecules

DOI: 10.1016/j.ijbiomac.2026.152439