Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli.

TitleStructural systems biology evaluation of metabolic thermotolerance in Escherichia coli.
Publication TypeJournal Article
Year of Publication2013
AuthorsChang RL, Andrews K, Kim D, Li Z, Godzik A, Palsson BO
JournalScience
Volume340
Issue6137
Pagination1220-3
Date Published2013 Jun 7
ISSN1095-9203
KeywordsEscherichia coli, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Hot Temperature, Metabolic Networks and Pathways, Models, Biological, Protein Conformation, Systems Biology, Transcriptional Activation
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.

DOI10.1126/science.1234012
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/23744946?dopt=Abstract
PMCPMC3777776
Alternate JournalScience
PubMed ID23744946