Séminaire de Pierre Millard

Pierre Millard - Toulouse Biotechnology Institute

Dynamic 13C-fluxomics as a tool to identify and understand regulation of metabolism: Example of acetate overflow in Escherichia coli

Résumé :

Summary: Dynamic 13C-fluxomics is a valuable tool to investigate the functioning, control and regulation of metabolic networks. In this talk, I will present a 13C-fluxomics strategy we have set up to investigate fermentative metabolism in the bacterium Escherichia coli. Using this approach, we have shown that overflow of acetate, a seemingly toxic by-product of glycolytic metabolism in E. coli, is a reversible process that allows uncoupling of glycolysis from the TCA cycle. We built and validated a predictive kinetic model of glucose and acetate metabolisms that reconciliates current observations and provides comprehensive understanding of the control and regulation of the acetate flux. We also found that, in turns, acetate regulates E. coli metabolism, and we investigated the timing and mechanisms of regulation by acetate. Finally, experimental evaluation of model-driven hypotheses showed that acetate, far to be toxic, improves robustness of E. coli to glycolytic perturbations and boosts its growth when the glycolytic flux is low.