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Article Dans Une Revue Nature Chemical Biology Année : 2023

Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling

Résumé

Anaerobic microbial metabolism drives critical functions within global ecosystems, host–microbiota interactions, and industrial applications, yet remains ill-defined. Here we advance a versatile approach to elaborate cellular metabolism in obligate anaerobes using the pathogen Clostridioides difficile , an amino acid and carbohydrate-fermenting Clostridia . High-resolution magic angle spinning nuclear magnetic resonance (NMR) spectroscopy of C. difficile , grown with fermentable 13 C substrates, informed dynamic flux balance analysis (dFBA) of the pathogen’s genome-scale metabolism. Analyses identified dynamic recruitment of oxidative and supporting reductive pathways, with integration of high-flux amino acid and glycolytic metabolism at alanine’s biosynthesis to support efficient energy generation, nitrogen handling and biomass generation. Model predictions informed an approach leveraging the sensitivity of 13 C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow from [U- 13 C]glucose and [ 15 N]leucine, confirming the formation of [ 13 C, 15 N]alanine. Findings identify metabolic strategies used by C. difficile to support its rapid colonization and expansion in gut ecosystems.
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pasteur-04145606 , version 1 (29-06-2023)

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Aidan Pavao, Brintha Girinathan, Johann Peltier, Pamela Altamirano Silva, Bruno Dupuy, et al.. Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling. Nature Chemical Biology, 2023, 19 (5), pp.556-564. ⟨10.1038/s41589-023-01275-9⟩. ⟨pasteur-04145606⟩
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