Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Over the past 15 years, Lytic Polysaccharide Monooxygenases (LPMOs) have emerged as crucial enzymes for valorizing recalcitrant polysaccharides [1]. These copper-containing enzymes employ an oxidative mechanism to cleave polysaccharide chains, using either O₂ (and electrons) or H₂O₂ (Fig. 1) [2]. Their active site features a mononuclear copper ion coordinated by the distinctive “histidine-brace” motif, where two histidine residues bind the metal ion, with the N-terminal histidine adopting an unusual bidentate coordination mode.

Figure 1. C1-oxidation of cellulose catalyzed by LPMO and structure of a LPMO with zoom on the active site.

Our research combines studies on enzymatic systems [3] and bioinspired model complexes [4]. A few years ago, our group developed low-molecular-weight synthetic models of LPMOs capable of promoting the oxidative cleavage of a soluble model substrate, para-nitrophenyl-β-D-glucopyranoside (p-NPG) [5]. Since then, numerous LPMO models have been reported, but comparing their activities remains challenging due to variations in substrates and reaction conditions. To address this, we developed two activity assays using soluble substrates in aqueous solutions under mild, near-neutral pH conditions. Additionally, we provided proof-of-concept that some bioinspired complexes can facilitate the oxidative depolymerization of insoluble polysaccharides [6]. This presentation will highlight our latest findings, focusing on strategies to rationalize catalytic activity across different LPMO models, providing possible guidance for designing efficient LPMO-inspired catalysts with potential applications in biomass conversion.

Acknowledgements: The authors are grateful to ECOS-NORD (M17P01) Region-Sud PACA and ANR fundings (INSPIRE ANR-23-CE43-0012 & LPMO-PEPS ANR-24-CE07-6490)