Functioning of a metabolic flux sensor in Escherichia coli

Karl Kochanowski, Benjamin Volkmer, Luca Gerosa, Bart R Haverkorn van Rijsewijk, Alexander Schmidt, Matthias Heinemann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Regulation of metabolic operation in response to extracellular cues is crucial for cells' survival. Next to the canonical nutrient sensors, which measure the concentration of nutrients, recently intracellular "metabolic flux" was proposed as a novel impetus for metabolic regulation. According to this concept, cells would have molecular systems ("flux sensors") in place that regulate metabolism as a function of the actually occurring metabolic fluxes. Although this resembles an appealing concept, we have not had any experimental evidence for the existence of flux sensors and also we have not known how these flux sensors would work in detail. Here, we show experimental evidence that supports the hypothesis that Escherichia coli is indeed able to measure its glycolytic flux and uses this signal for metabolic regulation. Combining experiment and theory, we show how this flux-sensing function could emerge from an aggregate of several molecular mechanisms: First, the system of reactions of lower glycolysis and the feedforward activation of fructose-1,6-bisphosphate on pyruvate kinase translate flux information into the concentration of the metabolite fructose-1,6-bisphosphate. The interaction of this "flux-signaling metabolite" with the transcription factor Cra then leads to flux-dependent regulation. By responding to glycolytic flux, rather than to the concentration of individual carbon sources, the cell may minimize sensing and regulatory expenses.

Original languageEnglish
Pages (from-to)1130-1135
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
Publication statusPublished - 15-Jan-2013


  • Escherichia coli K12
  • Feedback, Physiological
  • Fructose-Bisphosphatase
  • Genes, Bacterial
  • Glycolysis
  • Kinetics
  • Metabolic Networks and Pathways
  • Models, Biological
  • Pyruvate Kinase
  • Transcription, Genetic

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