2 research outputs found
A system-wide network reconstruction of gene regulation and metabolism in Escherichia coli
Genome-scale metabolic models have become a fundamental tool for examining
metabolic principles. However, metabolism is not solely characterized by the
underlying biochemical reactions and catalyzing enzymes, but also affected by
regulatory events. Since the pioneering work of Covert and co-workers as well
as Shlomi and co-workers it is debated, how regulation and metabolism
synergistically characterize a coherent cellular state. The first approaches
started from metabolic models which were extended by the regulation of the
encoding genes of the catalyzing enzymes. By now, bioinformatics databases in
principle allow addressing the challenge of integrating regulation and
metabolism on a system-wide level. Collecting information from several
databases we provide a network representation of the integrated gene regulatory
and metabolic system for Escherichia coli, including major cellular processes,
from metabolic processes via protein modification to a variety of regulatory
events. Besides transcriptional regulation, we also take into account
regulation of translation, enzyme activities and reactions. Our network model
provides novel topological characterizations of system components based on
their positions in the network. We show that network characteristics suggest a
representation of the integrated system as three network domains (regulatory,
metabolic and interface networks) instead of two. This new three-domain
representation reveals the structural centrality of components with known high
functional relevance. This integrated network can serve as a platform for
understanding coherent cellular states as active subnetworks and to elucidate
crossover effects between metabolism and gene regulation.Comment: 29 pages, 6 figures + Supplementary informatio