title: Heterogeneity in protein expression induces metabolic variability in a modeled Escherichia coli population.
abstract: Stochastic gene expression can lead to phenotypic differences among cells even in isogenic populations growing under macroscopically identical conditions. Here, we apply flux balance analysis in investigating the effects of single-cell proteomics data on the metabolic behavior of an in silico Escherichia coli population. We use the latest metabolic reconstruction integrated with transcriptional regulatory data to model realistic cells growing in a glucose minimal medium under aerobic conditions. The modeled population exhibits a broad distribution of growth rates, and principal component analysis was used to identify well-defined subpopulations that differ in terms of their pathway use. The cells differentiate into slow-growing acetate-secreting cells and fast-growing CO2-secreting cells, and a large population growing at intermediate rates shift from glycolysis to Entner-Doudoroff pathway use. Constraints imposed by integrating regulatory data have a large impact on NADH oxidizing pathway use within the cell. Finally, we find that stochasticity in the expression of only a few genes may be sufficient to capture most of the metabolic variability of the entire population.
authors.affiliation: Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Piyush
authors.initials: P
authors.lastname: Labhsetwar
authors.forename: John Andrew
authors.initials: JA
authors.lastname: Cole
authors.forename: Elijah
authors.initials: E
authors.lastname: Roberts
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Price
authors.forename: Zaida A
authors.initials: ZA
authors.lastname: Luthey-Schulten
mesh_terms: D000085:Acetates / Q000378:metabolism; D000465:Algorithms; D002245:Carbon Dioxide / Q000378:metabolism; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D040901:Proteomics / Q000379:methods; D013269:Stochastic Processes; D049490:Systems Biology / Q000379:methods
chemical_list: D000085:Acetates; D002245:Carbon Dioxide
keywords: aerobic regulation; metabolism; pathway utilization; protein noise; systems biology
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