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|
|Date Published||2013 Jun 7|
|Keywords||Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Hot Temperature, Metabolic Networks and Pathways, Models, Biological, Protein Conformation, Systems Biology, Transcriptional Activation|
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.