2025 FrenchBIC thesis prize to Rebecca LEBLAY
The 2025 thesis prize was awarded to Rebecca LEBLAY for her work on Bio-inspired complexes for the valorisation of recalcitrant polysaccharides. Her thesis was defended on 18th of October 2024. Project led under the supervision of Dr. A.J. Simaan and Dr. B. Faure at the BiosCiences laboratory in Marseille (BiosCiences | institut des sciences moléculaires de Marseille).
My thesis developed a biomimetic approach for improved recalcitrant biomass valorization.
In a context of fossil resource scarcity, the chemical industry is looking at biomass as a sustainable and abundant alternative resource. However, the valorization of lignocellulosic biomass is currently done through polluting processes with a high cost and energy consumption.In Nature, plant cell wall polysaccharides are deconstructed by a pool of enzymes. Hydrolases and oxidases are working synergetically to release saccharides. Among them, the Lytic Polysaccharides MonoOxygenase (LPMO) have attracted attention for their ability to perform oxidative cleavage of the polysaccharides and reduce their recalcitrance. Oxidations are performed by a mononuclear copper active site with a peculiar first coordination sphere named the “histidine brace » motif and consisting of two histidines, including the N-terminal histidine bound both by the NH2 terminal and the imidazole side chain.
Inspired by the main structural and functional characteristics of LPMOs, I synthesized copper complexes with 3N-coordination environment. An important part of my work consisted in establishing LPMO-like activity assays in aqueous solutions at neutral pH, on substrates of increasing complexity. [1,2] This allowed screening of various copper complexes and comparison of their activity. Mechanistic studies were also conducted to trap and characterize reactive intermediates [3] and estimate the involvement of reactive oxygen species in the observed activities. A preliminary structure-function relationships was proposed with a correlation between the nuclearity of the copper-oxygen intermediates, the Cu(II)/Cu(I) redox potentials of the complexes and the reactivity observed. In addition promising activities of some mimics on real recalcitrant polysaccharides was obtained providing proof-of-concept that biomimetic approaches can be relevant for biomass valorization.
In a second part of the project, we also investigated peptide-based copper complexes. In particular, using a simple tripeptide (HPH) we investigated effect of the N-methylation of the imidazole side-chain of the terminal histidine observed in some fungal LPMOs. [4] Along with data obtained on the enzymatic systems, our results indicate that the post-translational modification protects the copper active site from oxidative damages. Finally, in collaboration with Dr. C. Hureau (LCC, Toulouse), we evaluated several peptide families modifying the nature of the amino acids, the geometry around the copper, the flexibility. This extensive screening study provided several highly promising candidates for future investigations.
[1] R. Leblay, R. Delgadillo-Ruíz, C. Decroos, C. Hureau, M. Réglier, I. Castillo, B. Faure, A. J. Simaan, ChemCatChem 2023, 15, e202300933. [2] Yongxing Wang, Rogelio Gomez Pineiro, Rébecca Leblay, Michel Giorgi, Sylvain Bertaina, Maylis Orio, Bruno Faure, Marius Réglier, A. Jalila Simaan, Chem. Eur. J. 2025,. [3] De Tovar, J.; Leblay, R.; Wang, Y.; Wojcik, L.; Thibon-Pourret, A.; Reglier, M.; Simaan, A. J.; Le Poul, Belle, C.; N. Chem. Sci. 2024. Copper–oxygen adducts: new trends in characterization and properties towards C–H activation. [4] in writingCurrent affiliation:
Industrial Biotechnology, Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
Supervisor : Pr. Lisbeth OlssonPast affiliation:
Master thesis: Matis, Reykjavik, Iceland
Supervisor : Dr. Bjorn thor Adalsteinsson
