title: Inactivation of metabolic genes causes short- and long-range dys-regulation in Escherichia coli metabolic network.
abstract: The metabolic network in E. coli can be severely affected by the inactivation of metabolic genes that are required to catabolize a nutrient (D-galactose). We hypothesized that the resulting accumulation of small molecules can yield local as well as systemic effects on the metabolic network. Analysis of metabolomics data in wild-type and D-galactose non-utilizing mutants, galT, galU and galE, reveal the large metabolic differences between the wild-type and the mutants when the strains were grown in D-galactose. Network mapping suggested that the enzymatic defects affected the metabolic modules located both at short- and long-ranges from the D-galactose metabolic module. These modules suggested alterations in glutathione, energy, nucleotide and lipid metabolism and disturbed carbon to nitrogen ratio in mutant strains. The altered modules are required for normal cell growth for the wild-type strain, explaining why the cell growth is inhibited in the mutants in the presence of D-galactose. Identification of these distance-based dys-regulations would enhance the systems level understanding of metabolic networks of microorganisms having importance in biomedical and biotechnological research.
authors.affiliation: Genome Center, University of California Davis, Davis, California, United States of America.
authors.forename: Dinesh Kumar
authors.initials: DK
authors.lastname: Barupal
authors.affiliation: Infection and Immunity Research Center, KRIBB and University of Science and Technology, Daejeon, Korea ; Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Metabolon, Inc., Durham, North Carolina, United States of America.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Karoly
authors.affiliation: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Sankar
authors.initials: S
authors.lastname: Adhya
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D020868:Gene Silencing; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D055432:Metabolomics; D008954:Models, Biological; D025341:Principal Component Analysis
chemical_list: D005690:Galactose