||Forazoline A: marine-derived polyketide with antifungal in vivo efficacy.
||Thomas P Wyche, Jeff S Piotrowski, Yanpeng Hou, Doug Braun, Raamesh Deshpande, Sean McIlwain, Irene M Ong, Chad L Myers, Ilia A Guzei, William M Westler, David R Andes, Tim S Bugni
||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.
||Angew. Chem. Int. Ed. Engl. 2014; 53:11583-6
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