ArticleMolecular microbiology2017
Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Identification and Characterisation of the Gene Cluster Governing Biosynthesis of the Anti-Mycobacterial Antibiotic Acidomycin.Microbial biotechnology · 2026Article
- A short peptide derived from late embryogenesis abundant proteins enhances acid tolerance in Escherichia coli via modulation of two-component regulatory systems.The FEBS journal · 2026Article
- A split ALFA tag-nanobody system for protein localization and proximity proteomics in mycobacteria.mBio · 2025Article
- Competitive fitness of Staphylococcus aureus against nasal commensals depends on biotin biosynthesis and acquisition.The ISME journal · 2025Article
- Discovery, characterization and mechanism of a Microbacterium esterase for key d-biotin chiral intermediate synthesis.Bioresources and bioprocessing · 2024Article
- Identification of genes associated with persistence inFrontiers in microbiology · 2024Article
- Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection.Nature microbiology · 2023Article
- Integrative proteomic and physiological analyses of the molecular response to dessication-stress inFrontiers in plant science · 2022Article
- Nitric Oxide-Dependent Electron Transport Chain Inhibition by the CytochromeAntimicrobial agents and chemotherapy · 2021Article
- Biochemical and structural characterization of the BioZ enzyme engaged in bacterial biotin synthesis pathway.Nature communications · 2021Article
- The primary step of biotin synthesis in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Investigation of ( S)-(-)-Acidomycin: A Selective Antimycobacterial Natural Product That Inhibits Biotin Synthase.ACS infectious diseases · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Loss of bioQ, the repressor of biotin biosynthesis, in the pyc::tn strain reverted biotin auxotrophy, as did reconstituting the last step of the pathway through heterologous expression of BioB and provision of its substrate DTB. The role of Pyc in biotin regulation required its catalytic activities and could be supported by M. tuberculosis Pyc. Quantitation of the kinetics of depletion of biotinylated proteins after biotin withdrawal revealed that Pyc is the most rapidly depleted biotinylated protein and metabolomics revealed a broad metabolic shift in wild type cells upon biotin withdrawal which was blunted in cell lacking Pyc. Our data indicate that mycobacterial cells monitor biotin sufficiency through a metabolic signal generated by dysfunction of a biotinylated protein of central metabolism.
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