The integrated response of primary metabolites to gene deletions and the environment
The integrated response of primary metabolites to gene deletions and the environment
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DOI：
10.1039/c2mb25423a
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Zamboni, Nicola
中科院分区：
文献类型：
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作者：
Ewald, Jennifer Christina;Matta, Tanja;Zamboni, Nicola
细胞内代谢物产生于基因组和环境因素的分子整合，这些因素共同决定了代谢活性。然而，目前尚不清楚基因型、营养物质、生长和通量如何相互作用影响全球代谢物浓度。在这里，我们使用定量代谢组学来评估环境和基因型对酵母细胞代谢物组成的综合影响。我们分析了在三个典型碳源上生长的34个酵母单酶敲除突变体，生成了400个独特代谢组样本的数据集。不同的碳源在全球范围内影响了中间体的浓度，直接影响是由于底物流入而改变热力学势（δ (r)G），间接影响是通过细胞调节。相反，酶缺失只引起病变上游代谢底物的局部积累。尽管通量和生长速率发生了变化，但在所有测试的扰动下，关键的生物合成前体和辅因子总体上是稳健的。
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 (Delta(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.