Vinaxanthone, a new FabI inhibitor from Penicillium sp.

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dc.contributor.authorC J Zheng-
dc.contributor.authorMi Jin Sohn-
dc.contributor.authorWon Gon Kim-
dc.date.accessioned2017-04-19T09:13:32Z-
dc.date.available2017-04-19T09:13:32Z-
dc.date.issued2009-
dc.identifier.issn0305-7453-
dc.identifier.uri10.1093/jac/dkp058ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/8901-
dc.description.abstractObjectives: Bacterial enoyl-ACP reductase (FabI) has been validated as a novel antibacterial target for tackling infections caused by multidrug-resistant pathogens. A few FabI inhibitors, however, are known. This study isolated a new FabI inhibitor from Penicillium sp. Methods: A screening programme led to the selection of a Penicillium sp. producing a strong FabI-inhibitory metabolite. The chemical structure of the isolated FabI inhibitor was elucidated by mass spectrometry and nuclear magnetic resonance spectral data. The antibacterial target of the inhibitor was validated by overexpression assays. Results: The isolated FabI inhibitor was elucidated to be vinaxanthone. It selectively inhibited Staphylococcus aureus FabI with an IC50 of 0.9 μM; it did not affect FabK, an enoyl-ACP reductase of Streptococcus pneumoniae. Consistent with its inhibition of FabI, the inhibitor prevented intracellular fatty acid synthesis while it did not affect protein biosynthesis. It also prevented the growth of S. aureus as well as methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus. Importantly, fabI -overexpressing S. aureus showed reduced susceptibility to the inhibitor compared with the wild-type strain, demonstrating that its antibacterial action is mediated by inhibition of FabI. Conclusions: Vinaxanthone is a new FabI-directed antibacterial of natural origin that could have potential for further development as a new anti-MRSA agent.-
dc.publisherOxford Univ Press-
dc.titleVinaxanthone, a new FabI inhibitor from Penicillium sp.-
dc.title.alternativeVinaxanthone, a new FabI inhibitor from Penicillium sp.-
dc.typeArticle-
dc.citation.titleJournal of Antimicrobial Chemotherapy-
dc.citation.number5-
dc.citation.endPage953-
dc.citation.startPage949-
dc.citation.volume63-
dc.contributor.affiliatedAuthorMi Jin Sohn-
dc.contributor.affiliatedAuthorWon Gon Kim-
dc.contributor.alternativeNameZheng-
dc.contributor.alternativeName손미진-
dc.contributor.alternativeName김원곤-
dc.identifier.bibliographicCitationJournal of Antimicrobial Chemotherapy, vol. 63, no. 5, pp. 949-953-
dc.identifier.doi10.1093/jac/dkp058-
dc.subject.keywordantibacterial-
dc.subject.keywordEnoyl-ACP reductase-
dc.subject.keywordfatty acid synthesis-
dc.subject.keywordstaphylococcus aureus-
dc.subject.keywordtarget validation-
dc.subject.localAntibacterials-
dc.subject.localantibacterials-
dc.subject.localantibacterial-
dc.subject.localAntibacterial-
dc.subject.localEnoyl-ACP reductase-
dc.subject.localenoyl-ACP reductase-
dc.subject.localfatty acid synthesis-
dc.subject.localFatty acid synthesis-
dc.subject.localStaphylococcus aureus-
dc.subject.localstaphylococcus aureus-
dc.subject.localtarget validation-
dc.subject.localTarget validation-
dc.subject.localTarget Validation-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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