title: Characterization of physiological responses to 22 gene knockouts in Escherichia coli central carbon metabolism.
abstract: Understanding the impact of gene knockouts on cellular physiology, and metabolism in particular, is centrally important to quantitative systems biology and metabolic engineering. Here, we present a comprehensive physiological characterization of wild-type Escherichia coli and 22 knockouts of enzymes in the upper part of central carbon metabolism, including the PTS system, glycolysis, pentose phosphate pathway and Entner-Doudoroff pathway. Our results reveal significant metabolic changes that are affected by specific gene knockouts. Analysis of collective trends and correlations in the data using principal component analysis (PCA) provide new, and sometimes surprising, insights into E. coli physiology. Additionally, by comparing the data-to-model predictions from constraint-based approaches such as FBA, MOMA and RELATCH we demonstrate the important role of less well-understood kinetic and regulatory effects in central carbon metabolism.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, 150 Academy St, Newark, DE 19716, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Long
authors.affiliation: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, 150 Academy St, Newark, DE 19716, USA.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Gonzalez
authors.affiliation: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, 150 Academy St, Newark, DE 19716, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Sandoval
authors.affiliation: Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, 150 Academy St, Newark, DE 19716, USA. Electronic address: mranton@udel.edu.
authors.forename: Maciek R
authors.initials: MR
authors.lastname: Antoniewicz
mesh_terms: D002244:Carbon / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D055786:Gene Knockout Techniques / Q000379:methods*; D008657:Metabolic Clearance Rate; D060847:Metabolic Engineering / Q000379:methods; D064688:Metabolic Flux Analysis / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological
chemical_list: D029968:Escherichia coli Proteins; D005227:Fatty Acids; D002244:Carbon
keywords: COBRA modeling; Cell physiology; Escherichia coli; Gene knockout; Metabolism