Bacterial adaptation through distributed sensing of metabolic fluxes

Oliver Kotte, Judith B Zaugg, Matthias Heinemann
2010 Molecular Systems Biology  
The recognition of carbon sources and the regulatory adjustments to recognized changes are of particular importance for bacterial survival in fluctuating environments. Despite a thorough knowledge base of Escherichia coli's central metabolism and its regulation, fundamental aspects of the employed sensing and regulatory adjustment mechanisms remain unclear. In this paper, using a differential equation model that couples enzymatic and transcriptional regulation of E. coli's central metabolism,
more » ... show that the interplay of known interactions explains in molecular-level detail the system-wide adjustments of metabolic operation between glycolytic and gluconeogenic carbon sources. We show that these adaptations are enabled by an indirect recognition of carbon sources through a mechanism we termed distributed sensing of intracellular metabolic fluxes. This mechanism uses two general motifs to establish flux-signaling metabolites, whose bindings to transcription factors form flux sensors. As these sensors are embedded in global feedback loop architectures, closed-loop self-regulation can emerge within metabolism itself and therefore, metabolic operation may adapt itself autonomously (not requiring upstream sensing and signaling) to fluctuating carbon sources.
doi:10.1038/msb.2010.10 pmid:20212527 pmcid:PMC2858440 fatcat:bpvn626tlfgllcxl7av2agjnii