ArticleFrontiers in microbiology2012
Functional characterization and evolution of the isotuberculosinol operon in Mycobacterium tuberculosis and related Mycobacteria.
Article in Frontiers in microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Encoded metabolic remodeling amplifies drug resistance in Mycobacterium tuberculosis.PLoS pathogens · 2026Article
- The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility inJournal of bacteriology · 2025Article
- The mevalonate pathway of isoprenoid biosynthesis supports metabolic flexibility inbioRxiv : the preprint server for biology · 2025Article
- Structures of Mycobacterium tuberculosis isoprenyl diphosphate synthase Rv2173 in substrate-bound forms.Acta crystallographica. Section F, Structural biology communications · 2025Article
- GrcC1 mediates low-level resistance to multiple drugs inMicrobiology spectrum · 2025Article
- Mycobacteria that cause tuberculosis have retained ancestrally acquired genes for the biosynthesis of chemically diverse terpene nucleosides.PLoS biology · 2024Article
- A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages.The Journal of clinical investigation · 2023Article
- Genetic Underpinnings of Carotenogenesis and Light-Induced Transcriptome Remodeling in the Opportunistic PathogenPathogens (Basel, Switzerland) · 2023Article
- Investigation of Acid-Base Catalysis in Halimadienyl Diphosphate Synthase Involved inACS bio & med chem Au · 2022Article
- The Reductive Dehydroxylation Catalyzed by IspH, a Source of Inspiration for the Development of Novel Anti-Infectives.Molecules (Basel, Switzerland) · 2022Review
- Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.PloS one · 2021Article
- Metabolite Profiling: A Tool for the Biochemical Characterisation ofMicroorganisms · 2019Review
- Arginine in the FARM and SARM: A Role in Chain-Length Determination for Arginine in the Aspartate-Rich Motifs of Isoprenyl Diphosphate Synthases fromMolecules (Basel, Switzerland) · 2018Article
- Fitness-compensatory mutations facilitate the spread of drug-resistant F15/LAM4/KZN and F28 Mycobacterium tuberculosis strains in KwaZulu-Natal, South Africa.Journal of genetics · 2017Article
- Article
- Characterization of an orphan diterpenoid biosynthetic operon from Salinispora arenicola.Journal of natural products · 2014Article
- Molecular profiling of Mycobacterium tuberculosis identifies tuberculosinyl nucleoside products of the virulence-associated enzyme Rv3378c.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids.Microbiology spectrum · 2014Article
- Functional conservation of the capacity for ent-kaurene biosynthesis and an associated operon in certain rhizobia.Journal of bacteriology · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Terpenoid metabolites are important to the cellular function, structural integrity, and pathogenesis of the human-specific pathogen Mycobacterium tuberculosis (Mtb). Genetic and biochemical investigations have indicated a role for the diterpenoid isotuberculosinol (isoTb) early in the infection process. There are only two genes (Rv3377c and Rv3378c) required for production of isoTb, yet these are found in what appears to be a five-gene terpenoid/isoprenoid biosynthetic operon. Of the three remaining genes (Rv3379c, Rv3382c, and Rv3383c), previous work has indicated that Rv3379c is an inactive pseudo-gene. Here we demonstrate that Rv3382c and Rv3383c encode biochemically redundant machinery for isoprenoid metabolism, encoding a functional 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (LytB) for isoprenoid precursor production and a geranylgeranyl diphosphate (GGPP) synthase, respectively, for which the Mtb genome contains other functional isozymes (Rv1110 and Rv0562, respectively). These results complete the characterization of the isoTb biosynthetic operon, as well as further elucidating isoprenoid metabolism in Mtb. In addition, we have investigated the evolutionary origin of this operon, revealing Mtb-specific conservation of the diterpene synthase genes responsible for isoTb biosynthesis, which supports our previously advanced hypothesis that isoTb acts as a human-specific pathogenic metabolite and is consistent with the human host specificity of Mtb. Intriguingly, our results revealed that many mycobacteria contain orthologs for both Rv3383c and Rv0562, suggesting a potentially important role for these functionally redundant GGPP synthases in the evolution of terpenoid/isoprenoid metabolism in the mycobacteria.
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