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

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...

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Bibliographic Details
Published in:Journal of biotechnology 2007-12, Vol.132 (4), p.359-374
Main Authors: Hardiman, Timo, Lemuth, Karin, Keller, Markus A., Reuss, Matthias, Siemann-Herzberg, Martin
Format: Article
Language:English
Subjects:
Bacterial Physiological Phenomena
Bioreactors - microbiology
Carbon - metabolism
Central carbon metabolism
Citric Acid Cycle - genetics
Citric Acid Cycle - physiology
cra Modulon
crp Modulon
Escherichia coli
Escherichia coli - metabolism
Fed-batch cultivation
Gene Expression Regulation
Glucose - metabolism
Metabolic flux analysis
Stringent response
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Summary: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.
ISSN:0168-1656
1873-4863
DOI:10.1016/j.jbiotec.2007.08.029