{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:16:35Z","timestamp":1767960995074,"version":"3.49.0"},"reference-count":33,"publisher":"Proceedings of the National Academy of Sciences","issue":"18","license":[{"start":{"date-parts":[[2007,10,24]],"date-time":"2007-10-24T00:00:00Z","timestamp":1193184000000},"content-version":"vor","delay-in-days":176,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>\n            Emergence of bacterial resistance is a major issue for all classes of antibiotics; therefore, the identification of new classes is critically needed. Recently we reported the discovery of platensimycin by screening natural product extracts using a target-based whole-cell strategy with antisense silencing technology in concert with cell free biochemical validations. Continued screening efforts led to the discovery of platencin, a novel natural product that is chemically and biologically related but different from platensimycin. Platencin exhibits a broad-spectrum Gram-positive antibacterial activity through inhibition of fatty acid biosynthesis. It does not exhibit cross-resistance to key antibiotic resistant strains tested, including methicillin-resistant\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            , vancomycin-intermediate\n            <jats:italic>S. aureus<\/jats:italic>\n            , and vancomycin-resistant\n            <jats:italic>Enterococci<\/jats:italic>\n            . Platencin shows potent\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy without any observed toxicity. It targets two essential proteins, \u03b2-ketoacyl-[acyl carrier protein (ACP)] synthase II (FabF) and III (FabH) with IC\n            <jats:sub>50<\/jats:sub>\n            values of 1.95 and 3.91 \u03bcg\/ml, respectively, whereas platensimycin targets only FabF (IC\n            <jats:sub>50<\/jats:sub>\n            = 0.13 \u03bcg\/ml) in\n            <jats:italic>S. aureus<\/jats:italic>\n            , emphasizing the fact that more antibiotics with novel structures and new modes of action can be discovered by using this antisense differential sensitivity whole-cell screening paradigm.\n          <\/jats:p>","DOI":"10.1073\/pnas.0700746104","type":"journal-article","created":{"date-parts":[[2007,4,25]],"date-time":"2007-04-25T02:19:26Z","timestamp":1177467566000},"page":"7612-7616","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":351,"title":["Discovery of platencin, a dual FabF and FabH inhibitor with\n            <i>in vivo<\/i>\n            antibiotic properties"],"prefix":"10.1073","volume":"104","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Srinivas","family":"Kodali","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Sang Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Andrew","family":"Galgoci","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Ronald","family":"Painter","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Karen","family":"Dorso","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Fred","family":"Racine","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Mary","family":"Motyl","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Lorraine","family":"Hernandez","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Elizabeth","family":"Tinney","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Steven L.","family":"Colletti","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Kithsiri","family":"Herath","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Richard","family":"Cummings","sequence":"additional","affiliation":[{"name":"*Merck Research Laboratories, Rahway, NJ 07065; and"}]},{"given":"Oscar","family":"Salazar","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n B\u00e1sica, Merck Sharp &amp; Dohme de Espa\u00f1a, S.A. 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