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Structure-activity relationships of an emerging family of fungal lytic polysaccharide monooxygenases

Periodic Reporting for period 1 - ARTFUL (Structure-activity relationships of an emerging family of fungal lytic polysaccharide monooxygenases)

Okres sprawozdawczy: 2017-04-01 do 2019-03-31

Sustainable production of fuels and chemicals from biomass (e.g. wood, straw…) is essential considering the societal and political demands for alternatives to petrochemical commodities. The main steps to obtain fuel from biomass include degrading biomass into simple molecules, and this achieved by enzymatic degradation. This step is however one of the major bottlenecks to achieve economically viable processes. Indeed, the very complex structure and heterogeneous composition of wood and other plants makes it difficult to degrade by available enzyme cocktails. In nature, filamentous fungi are among the most effective degraders of lignocellulosic biomass highlighting their potential as a source of novel and highly efficient carbohydrate-active enzymes. In this context, the Artful project main objective was to identify new enzymes with high potential of unlocking the conversion of biomass.
To uncover enzyme candidates, the approach consisted in the exploration of the enzyme composition of secretomes produced when fungi are cultured on lignocellulosic substrates. The exploration comprised genomic, transcriptomic and proteomic data analyses. One of the major results of Artful is the identification of new families of proteins of which nothing was known before the project. They were identified in the enzyme cocktails produced by cellulolytic fungi. Following their discovery, several proteins of these new families were cloned and produced to evaluate their exact activity. The biochemical characterization that was performed revealed an oxidative mode of action, which is copper-dependent and confirmed the activity of these enzymes, classified thereby as Lytic Polysaccharide MonoOxygenases (LPMOs). Also, the Artful project enabled to extend the study of these enzymes to their biological role, the first of its kind in the LPMO field. The benefits of the exploitation of R&D results are patented (n° EP18306418). Also, The Artful project enable me to attend several Scientific Conferences:
- GRC on Carbohydrate-active Enzymes for Glycan Conversions, Andover (USA), July 2019. Invited speaker.
- 13th Carbohydrate Bioengineering Meeting, Toulouse (France), May 2019. Poster
- 2nd LPMO Symposium, Marseille (France), November 2018. Oral presentation
- 14th European Conference on Fungal Genetics (ECFG14) Haifa (Israël), February 2018. Oral presentation
Overall, the Artful project combined to genetics studies driven by Dennis Thiele (Duke University School of Medicine, Durham, USA) shift the landscape of the LPMO field from a purely lignocellulolytic context, where they are used as enzymatic tools, to a better understanding of their biological role in vivo, especially, their involvement in copper homeostasis and virulence. Thus, it impacts a wide range of areas of expertise (plant pathogens, plant/fungal symbiosis, fungal human pathogens…).
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