{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T19:28:28Z","timestamp":1761766108109},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[1992,1,1]],"date-time":"1992-01-01T00:00:00Z","timestamp":694224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[1992,1]]},"abstract":"<jats:p>Thiolactomycin [(4S)(2E,5E)-2,4,6-trimethyl-3-hydroxy-2,5,7-octatriene- 4-thiolide] (TLM) is a unique antibiotic structure that inhibits dissociated type II fatty acid synthase systems but not the multifunctional type I fatty acid synthases found in mammals. We screened an Escherichia coli genomic library for recombinant plasmids that impart TLM resistance to a TLM-sensitive strain of E. coli K-12. Nine independent plasmids were isolated, and all possessed a functional beta-ketoacyl-acyl carrier protein synthase I gene (fabB) based on their restriction enzyme maps and complementation of the temperature-sensitive growth of a fabB15(Ts) mutant. A plasmid (pJTB3) was constructed that contained only the fabB open reading frame. This plasmid conferred TLM resistance, complemented the fabB(Ts) mutation, and directed the overproduction of synthase I activity. TLM selectively inhibited unsaturated fatty acid synthesis in vivo; however, synthase I was not the only TLM target, since supplementation with oleate to circumvent the cellular requirement for an active synthase I did not confer TLM resistance. Overproduction of the FabB protein resulted in TLM-resistant fatty acid biosynthesis in vivo and in vitro. These data show that beta-ketoacyl-acyl carrier protein synthase I is a major target for TLM and that increased expression of this condensing enzyme is one mechanism for acquiring TLM resistance. However, extracts from a TLM-resistant mutant (strain CDM5) contained normal levels of TLM-sensitive synthase I activity, illustrating that there are other mechanisms of TLM resistance.<\/jats:p>","DOI":"10.1128\/jb.174.2.508-513.1992","type":"journal-article","created":{"date-parts":[[2016,11,4]],"date-time":"2016-11-04T20:13:06Z","timestamp":1478290386000},"page":"508-513","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Overproduction of beta-ketoacyl-acyl carrier protein synthase I imparts thiolactomycin resistance to Escherichia coli K-12"],"prefix":"10.1128","volume":"174","author":[{"given":"J T","family":"Tsay","sequence":"first","affiliation":[{"name":"Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101."}]},{"given":"C O","family":"Rock","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101."}]},{"given":"S","family":"Jackowski","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101."}]}],"member":"235","reference":[{"key":"p_1","first-page":"3190","article-title":"Acyl carrier protein. 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