{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:28:20Z","timestamp":1772162900918,"version":"3.50.1"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Condensing enzymes are essential in type II fatty acid synthesis and are promising targets for antibacterial drug discovery. Recently, a new approach using a xylose-inducible plasmid to express antisense RNA in\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    has been described; however, the actual mechanism was not delineated. In this paper, the mechanism of decreased target protein production by expression of antisense RNA was investigated using Northern blotting. This revealed that the antisense RNA acts posttranscriptionally by targeting mRNA, leading to 5\u2032 mRNA degradation. Using this technology, a two-plate assay was developed in order to identify FabF\/FabH target-specific cell-permeable inhibitors by screening of natural product extracts. Over 250,000 natural product fermentation broths were screened and then confirmed in biochemical assays, yielding a hit rate of 0.1%. All known natural product FabH and FabF inhibitors, including cerulenin, thiolactomycin, thiotetromycin, and Tu\u03083010, were discovered using this whole-cell mechanism-based screening approach. Phomallenic acids, which are new inhibitors of FabF, were also discovered. These new inhibitors exhibited target selectivity in the gel elongation assay and in the whole-cell-based two-plate assay. Phomallenic acid C showed good antibacterial activity, about 20-fold better than that of thiolactomycin and cerulenin, against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . It exhibited a spectrum of antibacterial activity against clinically important pathogens including methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    ,\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    , and\n                    <jats:italic>Haemophilus influenzae<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1128\/aac.50.2.519-526.2006","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T16:53:41Z","timestamp":1138208021000},"page":"519-526","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":181,"title":["Discovery of FabH\/FabF Inhibitors from Natural Products"],"prefix":"10.1128","volume":"50","author":[{"given":"Katherine","family":"Young","sequence":"first","affiliation":[{"name":"Merck Research Laboratories, Rahway, New Jersey 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