دورية أكاديمية
Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria
| العنوان: | Impact of the epoxide hydrolase EphD on the metabolism of mycolic acids in mycobacteria |
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| المؤلفون: | Madacki, Jan, Laval, Françoise, Grzegorzewicz, Anna, Lemassu, Anne, Záhorszká, Monika, Arand, Michael, Mcneil, Michael, Daffé, Mamadou, Jackson, Mary, Lanéelle, Marie-Antoinette, Korduláková, Jana |
| المساهمون: | Comenius University in Bratislava, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Colorado State University Fort Collins (CSU), Universität Zürich Zürich = University of Zurich (UZH) |
| المصدر: | ISSN: 0021-9258. |
| بيانات النشر: | HAL CCSD American Society for Biochemistry and Molecular Biology |
| سنة النشر: | 2018 |
| المجموعة: | Université Toulouse III - Paul Sabatier: HAL-UPS |
| مصطلحات موضوعية: | mycobacteria, cell wall, fatty acid metabolism, lipid, mass spectrometry (MS), bacterial cell envelope, epoxide hydrolase, epoxymycolic acid, mycolic acids, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] |
| الوصف: | International audience ; Mycolic acids are the hallmark of the cell envelope in myco-bacteria, which include the important human pathogens Myco-bacterium tuberculosis and Mycobacterium leprae. Mycolic acids are very long C60-C90 ␣-alkyl -hydroxy fatty acids having a variety of functional groups on their hydrocarbon chain that define several mycolate types. Mycobacteria also produce an unusually large number of putative epoxide hydrolases, but the physiological functions of these enzymes are still unclear. Here, we report that the mycobacterial epoxide hydrolase EphD is involved in mycolic acid metabolism. We found that orthologs of EphD from M. tuberculosis and M. smegmatis are functional epoxide hydrolases, cleaving a lipophilic substrate, 9,10-cis-ep-oxystearic acid, in vitro and forming a vicinal diol. The results of EphD overproduction in M. smegmatis and M. bovis BCG ⌬hma strains producing epoxymycolic acids indicated that EphD is involved in the metabolism of these forms of mycolates in both fast-and slow-growing mycobacteria. Moreover, using MALDI-TOF-MS and 1 H NMR spectroscopy of mycolic acids and lipids isolated from EphD-overproducing M. smegmatis, we identified new oxygenated mycolic acid species that accumulated during epoxymycolate depletion. Disruption of the ephD gene in M. tuberculosis specifically impaired the synthesis of ketomyco-lates and caused accumulation of their precursor, hydroxymy-colate, indicating either direct or indirect involvement of EphD in ketomycolate biosynthesis. Our results clearly indicate that EphD plays a role in metabolism of oxygenated mycolic acids in mycobacteria. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-02352263; https://hal.science/hal-02352263Test; https://hal.science/hal-02352263/documentTest; https://hal.science/hal-02352263/file/5172.full.pdfTest |
| DOI: | 10.1074/jbc.RA117.000246 |
| الإتاحة: | https://doi.org/10.1074/jbc.RA117.000246Test https://hal.science/hal-02352263Test https://hal.science/hal-02352263/documentTest https://hal.science/hal-02352263/file/5172.full.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.10655939 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.RA117.000246 |
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