title: Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.
abstract: Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine-invertebrate-associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of (13)C-(13)C gCOSY and (13)C-(15)N HMQC NMR data provided the direct carbon-carbon and carbon-nitrogen connectivity, respectively. This approach represents the first example of determining direct (13)C-(15)N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.
authors.affiliation: Pharmaceutical Sciences Division, University of Wisconsin-Madison, Madison, WI 53705 (USA).
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Wyche
authors.forename: Jeff S
authors.initials: JS
authors.lastname: Piotrowski
authors.forename: Yanpeng
authors.initials: Y
authors.lastname: Hou
authors.forename: Doug
authors.initials: D
authors.lastname: Braun
authors.forename: Raamesh
authors.initials: R
authors.lastname: Deshpande
authors.forename: Sean
authors.initials: S
authors.lastname: McIlwain
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ong
authors.forename: Chad L
authors.initials: CL
authors.lastname: Myers
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Guzei
authors.forename: William M
authors.initials: WM
authors.lastname: Westler
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.forename: Tim S
authors.initials: TS
authors.lastname: Bugni
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D008386:Marine Biology; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D061065:Polyketides / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D061065:Polyketides; C000598460:forazoline A
keywords: NMR spectroscopy; antifungal agents; genomics; natural products; structure elucidation