title: The integrated response of primary metabolites to gene deletions and the environment.
abstract: Intracellular metabolites arise from the molecular integration of genomic and environmental factors that jointly determine metabolic activity. However, it is not clear how the interplay of genotype, nutrients, growth, and fluxes affect metabolite concentrations globally. Here we used quantitative metabolomics to assess the combined effect of environment and genotype on the metabolite composition of a yeast cell. We analyzed a panel of 34 yeast single-enzyme knockout mutants grown on three archetypical carbon sources, generating a dataset of 400 unique metabolome samples. The different carbon sources globally affected the concentrations of intermediates, both directly, by changing the thermodynamic potentials (Δ(r)G) as a result of the substrate influx, and indirectly, by cellular regulation. In contrast, enzyme deletion elicited only local accumulation of the metabolic substrate immediately upstream of the lesion. Key biosynthetic precursors and cofactors were generally robust under all tested perturbations in spite of changes in fluxes and growth rate.
authors: Institute of Molecular Systems Biology, ETH Zurich, Wolfgang-Pauli Strasse 16, 8093 Zurich, Switzerland.
authors: Jennifer Christina
authors: JC
authors: Ewald
authors: Tanja
authors: T
authors: Matt
authors: Nicola
authors: N
authors: Zamboni
mesh_terms: D050260:Carbohydrate Metabolism / Q000235:genetics; D000431:Ethanol / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D017353:Gene Deletion; D059647:Gene-Environment Interaction; D005947:Glucose / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D007527:Isoenzymes; D029701:Saccharomyces cerevisiae Proteins; D000431:Ethanol; D005947:Glucose; D005690:Galactose