Transcriptional regulation in constraints-based metabolic models of Escherichia coli.

TitleTranscriptional regulation in constraints-based metabolic models of Escherichia coli.
Publication TypeJournal Article
Year of Publication2002
AuthorsCovert MW, Palsson BØ
JournalJ Biol Chem
Volume277
Issue31
Pagination28058-64
Date Published2002 Aug 2
ISSN0021-9258
KeywordsAerobiosis, Anaerobiosis, Escherichia coli, Gene Expression Regulation, Bacterial, Genome, Bacterial, Glucose, Lactose, Models, Biological, Models, Genetic, Transcription, Genetic
Abstract

Full genome sequences enable the construction of genome-scale in silico models of complex cellular functions. Genome-scale constraints-based models of Escherichia coli metabolism have been constructed and used to successfully interpret and predict cellular behavior under a range of conditions. These previous models do not account for regulation of gene transcription and thus cannot accurately predict some organism functions. Here we present an in silico model of the central E. coli metabolism that accounts for regulation of gene expression. This model accounts for 149 genes, the products of which include 16 regulatory proteins and 73 enzymes. These enzymes catalyze 113 reactions, 45 of which are controlled by transcriptional regulation. The combined metabolic/regulatory model can predict the ability of mutant E. coli strains to grow on defined media as well as time courses of cell growth, substrate uptake, metabolic by-product secretion, and qualitative gene expression under various conditions, as indicated by comparison with experimental data under a variety of environmental conditions. The in silico model may also be used to interpret dynamic behaviors observed in cell cultures. This combined metabolic/regulatory model is thus an important step toward the goal of synthesizing genome-scale models that accurately represent E. coli behavior.

DOI10.1074/jbc.M201691200
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/12006566?dopt=Abstract
Alternate TitleJ. Biol. Chem.
PubMed ID12006566