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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.

SUBMITTER: Wyche TP

PROVIDER: S-EPMC4215405 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.

Wyche Thomas P TP Piotrowski Jeff S JS Hou Yanpeng Y Braun Doug D Deshpande Raamesh R McIlwain Sean S Ong Irene M IM Myers Chad L CL Guzei Ilia A IA Westler William M WM Andes David R DR Bugni Tim S TS

Angewandte Chemie (International ed. in English) 20140904 43

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 natu ...[more]

PMID: 25197007

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