Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms12527
Title: A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria
Authors: Murima, P
Zimmermann, M
Chopra, T
Pojer, F
Fonti, G
Dal Peraro, M
Alonso, S 
Sauer, U
Pethe, K
McKinney, J.D
Keywords: carbon
glyoxylic acid
isocitrate lyase
bacterial protein
carbon
fatty acid
glyoxylic acid derivative
isocitrate dehydrogenase
bifurcation
carbon flux
chemotherapy
coliform bacterium
enzyme activity
fatty acid
infectivity
metabolism
partitioning
pathogenicity
steady-state equilibrium
tuberculosis
allosterism
Article
bacterial growth
bacterial strain
biosynthesis
carbon source
citric acid cycle
controlled study
energy metabolism
energy yield
enzyme phosphorylation
Escherichia coli
fatty acid metabolism
Mycobacterium tuberculosis
nonhuman
regulatory mechanism
tuberculosis
biological model
carbon cycle
classification
kinetics
metabolism
Mycobacterium
species difference
Corynebacterineae
Escherichia coli
Mycobacterium tuberculosis
Bacterial Proteins
Carbon
Carbon Cycle
Citric Acid Cycle
Fatty Acids
Glyoxylates
Isocitrate Dehydrogenase
Isocitrate Lyase
Kinetics
Models, Biological
Mycobacterium
Species Specificity
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Murima, P, Zimmermann, M, Chopra, T, Pojer, F, Fonti, G, Dal Peraro, M, Alonso, S, Sauer, U, Pethe, K, McKinney, J.D (2016). A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria. Nature Communications 7 : 12527. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms12527
Rights: Attribution 4.0 International
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. © The Author(s) 2016.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/182436
ISSN: 2041-1723
DOI: 10.1038/ncomms12527
Rights: Attribution 4.0 International
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