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Topology of the global regulatory network of carbon limitation in Escherichia coli

Paper ID Volume ID Publish Year Pages File Format Full-Text
25010 43552 2007 16 PDF Available
Title
Topology of the global regulatory network of carbon limitation in Escherichia coli
Abstract

One fundamental shortcoming of biotechnological processes operating under carbon-limiting conditions is the high-energy demand (maintenance) of the cells. Although the function of the central carbon metabolism in supplying precursors and energy for biosynthesis has been thoroughly characterized, its regulation and dynamic behaviour during carbon-limited growth has not yet been revealed. The current work demonstrates a time series of metabolic flux distributions during fed-batch cultivation of Escherichia coli K-12 W3110 applying a constant feed rate. The fluxes in glycolysis, pentose phosphate pathway and biosynthesis fell significantly, whereas TCA cycle fluxes remained constant. The flux redistribution resulted in an enhanced energy generation in the TCA cycle and consequently, in a 20% lower biomass yield. The intracellular alarmones ppGpp and cAMP accumulated in large quantities after the onset of nutrient limitation, subsequently declining to basal levels. The network topology of the regulation of the central metabolic pathways was identified so that the observed metabolic and regulatory behaviour can be described. This provides novel aspects of global regulation of the metabolism by the cra, crp and relA/spoT modulons. The work constitutes an important step towards dynamic mathematical modelling of regulation and metabolism, which is needed for the rational optimization of biotechnological processes.

Keywords
cra Modulon; crp Modulon; Stringent response; Central carbon metabolism; Fed-batch cultivation; Metabolic flux analysis
First Page Preview
Topology of the global regulatory network of carbon limitation in Escherichia coli
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 132, Issue 4, 1 December 2007, Pages 359–374
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering