Open AccessOptimal regulatory strategies for metabolic pathways in Escherichia coli depending on protein costs
Author(s) -
Wessely Frank,
Bartl Martin,
Guthke Reinhard,
Li Pu,
Schuster Stefan,
Kaleta Christoph
Publication year - 2011
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.1038/msb.2011.46
Subject(s) - biology , transcriptional regulation , computational biology , escherichia coli , systems biology , inference , flux (metallurgy) , regulation of gene expression , gene regulatory network , gene , genetics , transcription factor , computer science , gene expression , materials science , artificial intelligence , metallurgy
While previous studies have shed light on the link between the structure of metabolism and its transcriptional regulation, the extent to which transcriptional regulation controls metabolism has not yet been fully explored. In this work, we address this problem by integrating a large number of experimental data sets with a model of the metabolism of Escherichia coli . Using a combination of computational tools including the concept of elementary flux patterns, methods from network inference and dynamic optimization, we find that transcriptional regulation of pathways reflects the protein investment into these pathways. While pathways that are associated to a high protein cost are controlled by fine‐tuned transcriptional programs, pathways that only require a small protein cost are transcriptionally controlled in a few key reactions. As a reason for the occurrence of these different regulatory strategies, we identify an evolutionary trade‐off between the conflicting requirements to reduce protein investment and the requirement to be able to respond rapidly to changes in environmental conditions.