Bacterial adaptation through distributed sensing of metabolic fluxes
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Author / Creator
Date
2010-01
Publication Type
Journal Article
ETH Bibliography
yes
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Abstract
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.
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Publication status
published
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Book title
Journal / series
Volume
6 (1)
Pages / Article No.
355
Publisher
Nature
Event
Edition / version
Methods
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Date collected
Date created
Subject
computational model; metabolism; regulation; sensing; systems biology
Organisational unit
03713 - Sauer, Uwe / Sauer, Uwe