Ewald JC Matt T Zamboni N 2013 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. https://sonar.ch/global/documents/293029 eng info:eu-repo/semantics/altIdentifier/doi/10.1039/c2mb25423a info:eu-repo/semantics/altIdentifier/pmid/23340584 Molecular bioSystems. - 2013 Carbohydrate Metabolism Ethanol Galactose Gene Deletion Gene-Environment Interaction Glucose Isoenzymes Metabolic Networks and Pathways Metabolome Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Thermodynamics The integrated response of primary metabolites to gene deletions and the environment. http://purl.org/coar/resource_type/c_6501