Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli.
Title | Structural systems biology evaluation of metabolic thermotolerance in Escherichia coli. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Chang RL, Andrews K, Kim D, Li Z, Godzik A, Palsson BO |
Journal | Science |
Volume | 340 |
Issue | 6137 |
Pagination | 1220-3 |
Date Published | 2013 Jun 7 |
ISSN | 1095-9203 |
Keywords | Escherichia 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. |
DOI | 10.1126/science.1234012 |
PubMed URL | http://www.ncbi.nlm.nih.gov/pubmed/23744946?dopt=Abstract |
PMC | PMC3777776 |
Alternate Journal | Science |
PubMed ID | 23744946 |