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.