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Forazoline A: Marine‐Derived Polyketide with Antifungal In Vivo Efficacy
Author(s) -
Wyche Thomas P.,
Piotrowski Jeff S.,
Hou Yanpeng,
Braun Doug,
Deshpande Raamesh,
McIlwain Sean,
Ong Irene M.,
Myers Chad L.,
Guzei Ilia A.,
Westler William M.,
Andes David R.,
Bugni Tim S.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201405990
Subject(s) - polyketide , natural product , antifungal , chemistry , yeast , metabolomics , in vivo , stereochemistry , bacteria , candida albicans , marine invertebrates , computational biology , biology , biochemistry , microbiology and biotechnology , biosynthesis , gene , genetics , ecology , chromatography
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.