title: Overflow metabolism in Escherichia coli results from efficient proteome allocation.
abstract: Overflow metabolism refers to the seemingly wasteful strategy in which cells use fermentation instead of the more efficient respiration to generate energy, despite the availability of oxygen. Known as the Warburg effect in the context of cancer growth, this phenomenon occurs ubiquitously for fast-growing cells, including bacteria, fungi and mammalian cells, but its origin has remained unclear despite decades of research. Here we study metabolic overflow in Escherichia coli, and show that it is a global physiological response used to cope with changing proteomic demands of energy biogenesis and biomass synthesis under different growth conditions. A simple model of proteomic resource allocation can quantitatively account for all of the observed behaviours, and accurately predict responses to new perturbations. The key hypothesis of the model, that the proteome cost of energy biogenesis by respiration exceeds that by fermentation, is quantitatively confirmed by direct measurement of protein abundances via quantitative mass spectrometry.
authors.affiliation: Department of Physics, University at San Diego, La Jolla, of California California 92093-0374, USA.|Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Basan
authors.affiliation: Department of Physics, University at San Diego, La Jolla, of California California 92093-0374, USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Hui
authors.affiliation: Department of Physics, University at San Diego, La Jolla, of California California 92093-0374, USA.|Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okano
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA.
authors.forename: Zhongge
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Integrative Structural and Computational Biology, Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Williamson
authors.affiliation: Department of Physics, University at San Diego, La Jolla, of California California 92093-0374, USA.|Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093 USA.|Institute for Theoretical Studies, ETH Zürich, 8092 Zürich, Switzerland.
authors.forename: Terence
authors.initials: T
authors.lastname: Hwa
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D018533:Biomass; D019069:Cell Respiration; D004734:Energy Metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005285:Fermentation; D013058:Mass Spectrometry; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics
chemical_list: D029968:Escherichia coli Proteins; D020543:Proteome; D019342:Acetic Acid; D010100:Oxygen