{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:12:08Z","timestamp":1791461528863,"version":"4.3.4"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,9,11]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    fatty acid synthase type II (FAS-II) system has the unique property of producing unusually long-chain fatty acids involved in the biosynthesis of mycolic acids, key molecules of the tubercle bacillus. The enzyme(s) responsible for dehydration of (3\n                    <jats:italic>R<\/jats:italic>\n                    )-hydroxyacyl-ACP during the elongation cycles of the mycobacterial FAS-II remained unknown. This step is classically catalyzed by FabZ- and FabA-type enzymes in bacteria, but no such proteins are present in mycobacteria. Bioinformatic analyses and an essentiality study allowed the identification of a candidate protein cluster, Rv0635-Rv0636-Rv0637. Its expression in recombinant\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    strains leads to the formation of two heterodimers, Rv0635-Rv0636 (HadAB) and Rv0636-Rv0637 (HadBC), which also occurs in\n                    <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                    , as shown by split-Trp assays. Both heterodimers exhibit the enzymatic properties expected for mycobacterial FAS-II dehydratases: a marked specificity for both long-chain (\u2265C\n                    <jats:sub>12<\/jats:sub>\n                    ) and ACP-linked substrates. Furthermore, they function as 3-hydroxyacyl dehydratases when coupled with MabA and InhA enzymes from the\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    FAS-II system. HadAB and HadBC are the long-sought (3\n                    <jats:italic>R<\/jats:italic>\n                    )-hydroxyacyl-ACP dehydratases. The correlation between the substrate specificities of these enzymes, the organization of the orthologous gene cluster in different\n                    <jats:italic>Corynebacterineae<\/jats:italic>\n                    , and the structure of their mycolic acids suggests distinct roles for both heterodimers during the elongation process. This work describes bacterial monofunctional (3\n                    <jats:italic>R<\/jats:italic>\n                    )-hydroxyacyl-ACP dehydratases belonging to the hydratase 2 family. Their original structure and the fact that they are essential for\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    survival make these enzymes very good candidates for the development of antimycobacterial drugs.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0704132104","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T21:39:58Z","timestamp":1189028398000},"page":"14628-14633","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":144,"title":["The missing piece of the type II fatty acid synthase system from\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1073","volume":"104","author":[{"given":"Emmanuelle","family":"Sacco","sequence":"first","affiliation":[{"name":"*D\u00e9partement des M\u00e9canismes Mol\u00e9culaires des Infections Mycobact\u00e9riennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 31077 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Suarez","family":"Covarrubias","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"O'Hare","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences and Engineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, CH-1015 Lausanne, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Carroll","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease, Institute of Cell and Molecular Science at Barts and The London, London E1 2AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Eynard","sequence":"additional","affiliation":[{"name":"*D\u00e9partement des M\u00e9canismes Mol\u00e9culaires des Infections Mycobact\u00e9riennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 31077 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Alwyn","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Parish","sequence":"additional","affiliation":[{"name":"Centre for Infectious Disease, Institute of Cell and Molecular Science at Barts and The London, London E1 2AT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamadou","family":"Daff\u00e9","sequence":"additional","affiliation":[{"name":"*D\u00e9partement des M\u00e9canismes Mol\u00e9culaires des Infections Mycobact\u00e9riennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 31077 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"B\u00e4ckbro","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, SE-751 24 Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u00efk","family":"Qu\u00e9mard","sequence":"additional","affiliation":[{"name":"*D\u00e9partement des M\u00e9canismes Mol\u00e9culaires des Infections Mycobact\u00e9riennes, Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, 31077 Toulouse, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,9,11]]},"reference":[{"key":"e_1_3_4_1_2","volume-title":"Anti-Tuberculosis Drug Resistance in the World, Report No. 3","year":"2004","unstructured":"Anti-Tuberculosis Drug Resistance in the World, Report No. 3 (WHO, Geneva, 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