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Title: A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria
Authors: Murima, Paul
Zimmermann, Michael
Chopra, Tarun
Pojer, Florence
Fonti, Giulia
Dal Peraro, Matteo
Alonso, Sylvie
Sauer, Uwe
Pethe, Kevin
McKinney, John D.
Keywords: Bacterial genetics
Biochemical networks
Issue Date: 2016
Source: Murima, P., Zimmermann, M., Chopra, T., Pojer, F., Fonti, G., Dal Peraro, M., et al. (2016). A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria. Nature Communications, 7, 12527, 1-13.
Series/Report no.: Nature Communications
Abstract: Fatty acid metabolism is an important feature of the pathogenicity of Mycobacterium tuberculosis during infection. Consumption of fatty acids requires regulation of carbon flux bifurcation between the oxidative TCA cycle and the glyoxylate shunt. In Escherichia coli, flux bifurcation is regulated by phosphorylation-mediated inhibition of isocitrate dehydrogenase (ICD), a paradigmatic example of post-translational mechanisms governing metabolic fluxes. Here, we demonstrate that, in contrast to E. coli, carbon flux bifurcation in mycobacteria is regulated not by phosphorylation but through metabolic cross-activation of ICD by glyoxylate, which is produced by the glyoxylate shunt enzyme isocitrate lyase (ICL). This regulatory circuit maintains stable partitioning of fluxes, thus ensuring a balance between anaplerosis, energy production, and precursor biosynthesis. The rheostat-like mechanism of metabolite-mediated control of flux partitioning demonstrates the importance of allosteric regulation during metabolic steady-state. The sensitivity of this regulatory mechanism to perturbations presents a potentially attractive target for chemotherapy.
ISSN: 2041-1723
DOI: 10.1038/ncomms12527
Schools: School of Biological Sciences 
Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © The Authors 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles
SBS Journal Articles

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