Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli

Roger L. Chang, Kathleen Andrews, Donghyuk Kim, Zhanwen Li, Adam Godzik, Bernhard O. Palsson

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Genome-scale network reconstruction has enabled predictive modeling of metabolism for many systems. Traditionally, protein structural information has not been represented in such reconstructions. Expansion of 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. This analysis allowed the prediction of protein activities that limit network function at superoptimal temperatures 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 superoptimal temperatures. Inclusion of structural information expanded the content and predictive capability of genome-scale metabolic networks that enable structural systems biology of metabolism.

Original languageEnglish (US)
Pages (from-to)1220-1223
Number of pages4
JournalScience
Volume340
Issue number6137
DOIs
StatePublished - 2013
Externally publishedYes

ASJC Scopus subject areas

  • General

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