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Issue 3, 2013
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The integrated response of primary metabolites to gene deletions and the environment

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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 (ΔrG) 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.

Graphical abstract: The integrated response of primary metabolites to gene deletions and the environment

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Publication details

The article was received on 09 Oct 2012, accepted on 18 Dec 2012 and first published on 19 Dec 2012


Article type: Paper
DOI: 10.1039/C2MB25423A
Mol. BioSyst., 2013,9, 440-446

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    The integrated response of primary metabolites to gene deletions and the environment

    J. C. Ewald, T. Matt and N. Zamboni, Mol. BioSyst., 2013, 9, 440
    DOI: 10.1039/C2MB25423A

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