title: 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.
authors.affiliation: Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Chang
authors.forename: Kathleen
authors.initials: K
authors.lastname: Andrews
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.forename: Zhanwen
authors.initials: Z
authors.lastname: Li
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006358:Hot Temperature; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D011487:Protein Conformation; D049490:Systems Biology; D015533:Transcriptional Activation
chemical_list: D029968:Escherichia coli Proteins