Publication Date:
2013-06-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777776/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777776/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, Roger L -- Andrews, Kathleen -- Kim, Donghyuk -- Li, Zhanwen -- Godzik, Adam -- Palsson, Bernhard O -- R01 GM057089/GM/NIGMS NIH HHS/ -- R01 GM101457/GM/NIGMS NIH HHS/ -- R01GM101457/GM/NIGMS NIH HHS/ -- U54 GM094586/GM/NIGMS NIH HHS/ -- U54GM094586/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1220-3. doi: 10.1126/science.1234012.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA 92093-0412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744946" target="_blank"〉PubMed〈/a〉
Keywords:
Escherichia coli/*genetics/growth & development/*metabolism
;
Escherichia coli Proteins/chemistry/genetics/*metabolism
;
Gene Expression Regulation, Bacterial
;
*Hot Temperature
;
*Metabolic Networks and Pathways
;
Models, Biological
;
Protein Conformation
;
Systems Biology
;
Transcriptional Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
