Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli
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.
- Publication:
-
Science
- Pub Date:
- June 2013
- DOI:
- 10.1126/science.1234012
- Bibcode:
- 2013Sci...340.1220C
- Keywords:
-
- CELL BIOL Biochemistry, Genetics, Cell-Biology