Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli.

Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli.
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DOI:
10.1126/science.1234012
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发表时间:
2013-06-07
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Palsson BO
Palsson BO
中科院分区:
其他
文献类型:
--
作者:
Chang RL;Andrews K;Kim D;Li Z;Godzik A;Palsson BO

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Genome scale network reconstruction has enabled predictive modeling of metabolism for many systems. Traditionally, protein structural information has not been represented in such reconstructions. Expanding a genome-scale model of Escherichia coli metabolism by including experimental and predicted protein structures enabled the analysis of protein thermostability in a network context, allowing prediction of protein activities that limit network function at super-optimal temperature and mechanistic interpretations of mutations found in strains adapted to heat. Predicted growth-limiting factors for thermotolerance were validated through nutrient supplementation experiments and defined metabolic sensitivities to heat stress, providing evidence that metabolic enzyme thermostability is rate limiting at super-optimal temperature. Inclusion of structural information expanded the content and predictive capability of genome-scale metabolic networks enabling structural systems biology of metabolism.
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