ArticleMolecular microbiology2010
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest-4-en-3-one.
Article in Molecular microbiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 134 citations in OpenAlex.
- An adenylyl cyclase switch reroutes carbon from growth to virulence lipids inbioRxiv : the preprint server for biology · 2026Article
- Supporting activities of cognate redox partners for sterol-metabolizing P450 enzymes in Mycobacterium neoaurum.The Journal of biological chemistry · 2026Article
- Structure-Function Analysis ofInternational journal of molecular sciences · 2025Article
- Fragment-Based Development of Small Molecule Inhibitors TargetingJournal of medicinal chemistry · 2025Article
- Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy.Frontiers in cellular and infection microbiology · 2025Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Improving the production of 22-hydroxy-23,24-bisnorchol-4-ene-3-one in Mycolicibacterium smegmatis.Microbial biotechnology · 2024Article
- Drug metabolism of ciprofloxacin, ivacaftor, and raloxifene by Pseudomonas aeruginosa cytochrome P450 CYP107S1.The Journal of biological chemistry · 2024Article
- The role of cholesterol and its oxidation products in tuberculosis pathogenesis.Immunometabolism (Cobham, Surrey) · 2024Review
- Microbial metabolism of diosgenin by a novel isolated Mycolicibacterium sp. HK-90: A promising biosynthetic platform to produce 19-carbon and 21-carbon steroids.Microbial biotechnology · 2024Article
- Molecular Cloning, Heterologous Expression, Purification, and Evaluation of Protein-Ligand Interactions of CYP51 ofBiomedicines · 2023Article
- Unravelling and engineering an operon involved in the side-chain degradation of sterols in Mycolicibacterium neoaurum for the production of steroid synthons.Biotechnology for biofuels and bioproducts · 2023Article
- Structure Based Discovery of Inhibitors of CYP125 and CYP142 from Mycobacterium tuberculosis.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- Insight into Different Stages of Steroid Degradation in ThermophilicInternational journal of molecular sciences · 2022Article
- Rational development of mycobacteria cell factory for advancing the steroid biomanufacturing.World journal of microbiology & biotechnology · 2022Review
- An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism inMicroorganisms · 2022Article
- Steroid Metabolism in Thermophilic ActinobacteriumMicroorganisms · 2021Article
- Ancient Bacterial ClassInternational journal of molecular sciences · 2021Article
- Characterization of CYP125A13, the First Steroid C-27 Monooxygenase fromJournal of microbiology and biotechnology · 2020Article
- Microbial degradation of steroid sex hormones: implications for environmental and ecological studies.Microbial biotechnology · 2020Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The infectivity and persistence of Mycobacterium tuberculosis requires the utilization of host cell cholesterol. We have examined the specific role of cytochrome P450 CYP125A1 in the cholesterol degradation pathway using genetic, biochemical and high-resolution mass spectrometric approaches. The analysis of lipid profiles from cells grown on cholesterol revealed that CYP125A1 is required to incorporate the cholesterol side-chain carbon atoms into cellular lipids, as evidenced by an increase in the mass of the methyl-branched phthiocerol dimycocerosates. We observed that cholesterol-exposed cells lacking CYP125A1 accumulate cholest-4-en-3-one, suggesting that this is a physiological substrate for this enzyme. Reconstitution of enzymatic activity with spinach ferredoxin and ferredoxin reductase revealed that recombinant CYP125A1 indeed binds both cholest-4-en-3-one and cholesterol, efficiently hydroxylates both of them at C-27, and then further oxidizes 27-hydroxycholest-4-en-3-one to cholest-4-en-3-one-27-oic acid. We determined the X-ray structure of cholest-4-en-3-one-bound CYP125A1 at a resolution of 1.58 A. CYP125A1 is essential for growth of CDC1551 in media containing cholesterol or cholest-4-en-3-one. In its absence, the latter compound is toxic for both CDC1551 and H37Rv when added with glycerol as a second carbon source. CYP125A1 is a key enzyme in cholesterol metabolism and plays a crucial role in circumventing the deleterious effect of cholest-4-en-3-one.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.