title: Towards a systems level understanding of the oxygen response of Escherichia coli.
abstract: Escherichia coli is a facultatively anaerobic bacterium. With glucose if no external electron acceptors are available, ATP is produced by substrate level phosphorylation. The intracellular redox balance is maintained by mixed-acid fermentation, that is, the production and excretion of several organic acids. When oxygen is available, E. coli switches to aerobic respiration to achieve redox balance and optimal energy conservation by proton translocation linked to electron transfer. The switch between fermentative and aerobic respiratory growth is driven by extensive changes in gene expression and protein synthesis, resulting in global changes in metabolic fluxes and metabolite concentrations. This oxygen response is determined by the interaction of global and local genetic regulatory mechanisms, as well as by enzymatic regulation. The response is affected by basic physical constraints such as diffusion, thermodynamics and the requirement for a balance of carbon, electrons and energy (predominantly the proton motive force and the ATP pool). A comprehensive systems level understanding of the oxygen response of E. coli requires the integrated interpretation of experimental data that are pertinent to the multiple levels of organization that mediate the response. In the pan-European venture, Systems Biology of Microorganisms (SysMO) and specifically within the project Systems Understanding of Microbial Oxygen Metabolism (SUMO), regulator activities, gene expression, metabolite levels and metabolic flux datasets were obtained using a standardized and reproducible chemostat-based experimental system. These different types and qualities of data were integrated using mathematical models. The approach described here has revealed a much more detailed picture of the aerobic-anaerobic response, especially for the environmentally critical microaerobic range that is located between unlimited oxygen availability and anaerobiosis.
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany. Electronic address: bettenbrock@mpi-magdeburg.mpg.de.
authors.forename: Katja
authors.initials: K
authors.lastname: Bettenbrock
authors.affiliation: Department of Computer Science, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Hao
authors.initials: H
authors.lastname: Bai
authors.affiliation: Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ederer
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Green
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Hellingwerf
authors.affiliation: Department of Computer Science, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Holcombe
authors.affiliation: Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany.
authors.forename: Samantha
authors.initials: S
authors.lastname: Kunz
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Rolfe
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Guido
authors.initials: G
authors.lastname: Sanguinetti
authors.affiliation: Institute for System Dynamics, University of Stuttgart, Stuttgart, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sawodny
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sharma
authors.affiliation: Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Steinsiek
authors.affiliation: Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Poole
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D010100:Oxygen / Q000378:metabolism*; D049490:Systems Biology
chemical_list: D029968:Escherichia coli Proteins; D000255:Adenosine Triphosphate; D010100:Oxygen
keywords: Agent based model; Electron transport chain; Fermentation; Mathematical modeling; Metabolic fluxes; Oxygen sensing; Quinone; Redox balance; Respiration; Spatial organisation, Terminal oxidases; Transcription factor activities