Open AccessBacterial adaptation through distributed sensing of metabolic fluxes
Author(s) -
Kotte Oliver,
Zaugg Judith B,
Heinemann Matthias
Publication year - 2010
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.2010.10
Subject(s) - biology , carbon flux , adaptation (eye) , flux (metallurgy) , systems biology , mechanism (biology) , transcription factor , transcriptional regulation , metabolic pathway , computational biology , metabolism , regulation of gene expression , intracellular , microbiology and biotechnology , gene , biochemistry , ecology , neuroscience , physics , chemistry , ecosystem , organic chemistry , quantum mechanics
The recognition of carbon sources and the regulatory adjustments to recognized changes are of particular importance for bacterial survival in fluctuating environments. Despite a thorough knowledge base of Escherichia coli 's central metabolism and its regulation, fundamental aspects of the employed sensing and regulatory adjustment mechanisms remain unclear. In this paper, using a differential equation model that couples enzymatic and transcriptional regulation of E. coli 's central metabolism, we show that the interplay of known interactions explains in molecular‐level detail the system‐wide adjustments of metabolic operation between glycolytic and gluconeogenic carbon sources. We show that these adaptations are enabled by an indirect recognition of carbon sources through a mechanism we termed distributed sensing of intracellular metabolic fluxes. This mechanism uses two general motifs to establish flux‐signaling metabolites, whose bindings to transcription factors form flux sensors. As these sensors are embedded in global feedback loop architectures, closed‐loop self‐regulation can emerge within metabolism itself and therefore, metabolic operation may adapt itself autonomously (not requiring upstream sensing and signaling) to fluctuating carbon sources.