ArticleNature communications2016
A rheostat mechanism governs the bifurcation of carbon flux in mycobacteria.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Functional redundancy driven by isocitrate dehydrogenase enhances metabolic robustness in Pseudomonas putida KT2440.Microbial cell factories · 2026Article
- Study on the phosphorylation of NADJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- An integrated structural and biophysical approach to study carbon metabolism inQRB discovery · 2025Review
- Two Different Isocitrate Dehydrogenases fromInternational journal of molecular sciences · 2023Article
- The Native Microbiome MemberMetabolites · 2023Article
- Role of MHC class I pathways inFrontiers in cellular and infection microbiology · 2023Review
- A metabolic perspective into antimicrobial tolerance and resistance.The Lancet. Microbe · 2022Article
- Modulatory Impact of the sRNA Mcr11 in Two Clinical Isolates of Mycobacterium tuberculosis.Current microbiology · 2022Article
- Engineering the glyoxylate cycle for chemical bioproduction.Frontiers in bioengineering and biotechnology · 2022Review
- Regulation of theJournal of bacteriology · 2021Article
- Bedaquiline reprograms central metabolism to reveal glycolytic vulnerability in Mycobacterium tuberculosis.Nature communications · 2020Article
- Acetyl-CoA-mediated activation of Mycobacterium tuberculosis isocitrate lyase 2.Nature communications · 2019Article
- Article
- Central metabolic interactions of immune cells and microbes: prospects for defeating infections.EMBO reports · 2019Review
- Gluconeogenic precursor availability regulates flux through the glyoxylate shunt inThe Journal of biological chemistry · 2018Article
- Triacylglycerol: nourishing molecule in endurance of Mycobacterium tuberculosis.Journal of biosciences · 2018Review
- Article
- Amino Acids As Mediators of Metabolic Cross Talk between Host and Pathogen.Frontiers in immunology · 2018Review
- Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation inProceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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