This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nanchen, A.
Right arrow Articles by Sauer, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nanchen, A.
Right arrow Articles by Sauer, U.

 Previous Article  |  Next Article 

Journal of Bacteriology, April 2008, p. 2323-2330, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01353-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Cyclic AMP-Dependent Catabolite Repression Is the Dominant Control Mechanism of Metabolic Fluxes under Glucose Limitation in Escherichia coli{triangledown} ,{dagger}

Annik Nanchen, Alexander Schicker, Olga Revelles, and Uwe Sauer*

Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland

Received 19 August 2007/ Accepted 17 January 2008

Although a whole arsenal of mechanisms are potentially involved in metabolic regulation, it is largely uncertain when, under which conditions, and to which extent a particular mechanism actually controls network fluxes and thus cellular physiology. Based on 13C flux analysis of Escherichia coli mutants, we elucidated the relevance of global transcriptional regulation by ArcA, ArcB, Cra, CreB, CreC, Crp, Cya, Fnr, Hns, Mlc, OmpR, and UspA on aerobic glucose catabolism in glucose-limited chemostat cultures at a growth rate of 0.1 h–1. The by far most relevant control mechanism was cyclic AMP (cAMP)-dependent catabolite repression as the inducer of the phosphoenolpyruvate (PEP)-glyoxylate cycle and thus low tricarboxylic acid cycle fluxes. While all other mutants and the reference E. coli strain exhibited high glyoxylate shunt and PEP carboxykinase fluxes, and thus high PEP-glyoxylate cycle flux, this cycle was essentially abolished in both the Crp and Cya mutants, which lack the cAMP-cAMP receptor protein complex. Most other mutations were phenotypically silent, and only the Cra and Hns mutants exhibited slightly altered flux distributions through PEP carboxykinase and the tricarboxylic acid cycle, respectively. The Cra effect on PEP carboxykinase was probably the consequence of a specific control mechanism, while the Hns effect appears to be unspecific. For central metabolism, the available data thus suggest that a single transcriptional regulation process exerts the dominant control under a given condition and this control is highly specific for a single pathway or cycle within the network.

* Corresponding author. Mailing address: Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland. Phone: 41-44-633 3672. Fax: 41-44-633 1051. E-mail: sauer{at}imsb.biol.ethz.ch

{triangledown} Published ahead of print on 25 January 2008.

{dagger} Supplemental material for this article may be found at http://jb.asm.org/.

Journal of Bacteriology, April 2008, p. 2323-2330, Vol. 190, No. 7
0021-9193/08/$08.00+0     doi:10.1128/JB.01353-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nikel, P. I., Zhu, J., San, K.-Y., Mendez, B. S., Bennett, G. N. (2009). Metabolic Flux Analysis of Escherichia coli creB and arcA Mutants Reveals Shared Control of Carbon Catabolism under Microaerobic Growth Conditions. J. Bacteriol. 191: 5538-5548 [Abstract] [Full Text]  
  • Lemuth, K., Hardiman, T., Winter, S., Pfeiffer, D., Keller, M. A., Lange, S., Reuss, M., Schmid, R. D., Siemann-Herzberg, M. (2008). Global Transcription and Metabolic Flux Analysis of Escherichia coli in Glucose-Limited Fed-Batch Cultivations. Appl. Environ. Microbiol. 74: 7002-7015 [Abstract] [Full Text]  
  • Gorke, B., Vogel, J. (2008). Noncoding RNA control of the making and breaking of sugars. Genes Dev. 22: 2914-2925 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»