Genome-Guided Discovery of Antifungal Filipins from a Deep-Sea-Derived Streptomyces antibioticus .

Nine new ( 1 - 3 , 5 - 8 , 11 , and 12 ; named filipins VI-XIV) and three known ( 4 , 9 , and 10 ) filipin-type polyene macrolides were isolated from the deep-sea-derived Streptomyces antibioticus OUCT16-23 using a genome-guided strategy coupled with bioassay. Their structures were elucidated based on the extensive MS and NMR spectroscopic analyses together with ECD calculations. In an antifungal assay, compounds 4 , 5 , and 7 - 10 showed different degrees of growth inhibition against Candida albicans with minimum inhibitory concentrations (MICs) of 1.56-12.5 μg/mL, by which the alkyl side-chain substitution affecting the activity was preliminarily studied. A biosynthetic pathway to 1 - 12 in S. antibioticus OUCT16-23 is also proposed.