Genome-Guided Discovery of Antifungal Filipins from a Deep-Sea-Derived <i>Streptomyces antibioticus</i>
Yilei Bao, Huayue Li, Huayue Li, Yujing Dong, He Duan, Hongcheng Li, Hongcheng Li, Wenli Li
Abstract
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.