%0 Journal Article %1 ISI:000251494300004 %A Hardiman, Timo %A Lemuth, Karin %A Keller, Markus A. %A Reuss, Matthias %A Siemann-Herzberg, Martin %C PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS %D 2007 %I ELSEVIER SCIENCE BV %J JOURNAL OF BIOTECHNOLOGY %K analysis} carbon central crp cultivation; fed-batch flux metabolic metabolism; modulon; myown response; stringent {cra %N 4 %P 359-374 %R 10.1016/j.jbiotec.2007.08.029 %T Topology of the global regulatory network of carbon limitation in Escherichia coli %U https://doi.org/10.1016/j.jbiotec.2007.08.029 %V 132 %X 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. (c) 2007 Elsevier B.V. All rights reserved.

@article{ISI:000251494300004, 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. (c) 2007 Elsevier B.V. All rights reserved.}}, added-at = {2018-01-25T13:38:08.000+0100}, address = {{PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS}}, affiliation = {{Siemann-Herzberg, M (Reprint Author), Univ Stuttgart, Inst Biochem Engn, Allmandring 31, D-70569 Stuttgart, Germany. Univ Stuttgart, Inst Biochem Engn, D-70569 Stuttgart, Germany. Univ Stuttgart, Inst Tech Biochem, D-70569 Stuttgart, Germany.}}, author = {Hardiman, Timo and Lemuth, Karin and Keller, Markus A. and Reuss, Matthias and Siemann-Herzberg, Martin}, author-email = {{siemann@ibvt.uni-stuttgart.de}}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/29c861a1f10c8e36a58bf26d453514d64/siemannherzberg}, da = {{2018-01-25}}, doc-delivery-number = {{239BY}}, doi = {{10.1016/j.jbiotec.2007.08.029}}, interhash = {400049c6b506005528eff057fcdbe312}, intrahash = {9c861a1f10c8e36a58bf26d453514d64}, issn = {{0168-1656}}, journal = {{JOURNAL OF BIOTECHNOLOGY}}, journal-iso = {{J. Biotechnol.}}, keywords = {analysis} carbon central crp cultivation; fed-batch flux metabolic metabolism; modulon; myown response; stringent {cra}, keywords-plus = {{METABOLIC FLUX ANALYSIS; MULTIPARAMETER FLOW-CYTOMETRY; FED-BATCH CULTURES; SPOT GENE-PRODUCT; LIMITED FED-BATCH; IN-VITRO; TRANSCRIPTION INITIATION; STOICHIOMETRIC MODEL; PHYSIOLOGICAL-STATE; OVERFLOW METABOLISM}}, language = {{English}}, month = {{DEC 1}}, number = {{4}}, number-of-cited-references = {{77}}, pages = {{359-374}}, publisher = {{ELSEVIER SCIENCE BV}}, research-areas = {{Biotechnology \& Applied Microbiology}}, times-cited = {{45}}, timestamp = {2018-01-25T12:38:18.000+0100}, title = {{Topology of the global regulatory network of carbon limitation in Escherichia coli}}, type = {{Article}}, unique-id = {{ISI:000251494300004}}, url = {https://doi.org/10.1016/j.jbiotec.2007.08.029}, usage-count-last-180-days = {{0}}, usage-count-since-2013 = {{15}}, volume = {{132}}, web-of-science-categories = {{Biotechnology \& Applied Microbiology}}, year = {{2007}} }