Forazoline A: Marine-Derived Polyketide with Antifungal In Vivo Efficacy

ForazolineA, a novel antifungal polyketide with invivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine-invertebrate-associated bacteria. ForazolineA had a highly unusual and unprecedented skeleton. Acquisition of C-13-C-13 gCOSY and C-13-N-15 HMQCNMR data provided the direct carbon-carbon and carbon-nitrogen connectivity, respectively. This approach represents the first example of determining direct C-13-N-15 connectivity for a natural product. Using yeast chemical genomics, we propose that forazolineA operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.