RRC ID 35580
著者 Kochanowski K, Volkmer B, Gerosa L, Haverkorn van Rijsewijk BR, Schmidt A, Heinemann M.
タイトル Functioning of a metabolic flux sensor in Escherichia coli.
ジャーナル Proc Natl Acad Sci U S A
Abstract 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.
巻・号 110(3)
ページ 1130-5
公開日 2013-1-15
DOI 10.1073/pnas.1202582110
PII 1202582110
PMID 23277571
PMC PMC3549114
MeSH Escherichia coli K12 / genetics Escherichia coli K12 / metabolism* Feedback, Physiological Fructose-Bisphosphatase / metabolism Genes, Bacterial Glycolysis Kinetics Metabolic Networks and Pathways Models, Biological Pyruvate Kinase / genetics Pyruvate Kinase / metabolism Transcription, Genetic
IF 9.412
引用数 108
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
原核生物(大腸菌) ME9062(BW25113) JW1666-KC(pykF)