DSSS - Metabolic coordination through metabolite-protein interactions

Bacteria sense their environment primarily by detecting intracellular changes triggered by environmental stimuli. Since fluxes and metabolite levels respond within seconds, such rapid sensing is mediated by allosteric binding of metabolites to regulatory proteins and enzymes. Even for the presumably best characterized bacterium E. coli, however, we have rather limited understanding of how allosteric and post-translational metabolite-protein interactions drive phenotypic changes. Combining metabolomics, proteomics, flux analysis, and point mutations, I will show how phosphorylation and acetylation controls central metabolism. The harder problem of measuring the more fleeting, noncovalent metabolite binding, we address through physical binding assays and computational inference from the effects. Here, I will discuss the results of systematically elucidating functionality of metabolite binding in central metabolism of E. coli.