Cyclohumulanoid Sesquiterpenes Induced by the Noncompetitive Coculture of Phellinus orientoasiaticus and Xylodon flaviporus

Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitiveinteractions between test strains. During our LC-MS-basedchemical screening of randomized cocultures of Basidiomycetousfungi, we discovered that the coculture of Phellinus orientoasiaticus(Hymenochaetaceae) and Xylodon flaviporus(Schizoporaceae)induces multiple metabolites, although they did not show anycompetitive morphology. Targeted isolation yielded three newsesquiterpenes (1-3) along withfive known analogues (4-8).The structures of the isolates were determined by MS and NMRexperiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-,sterpurane-, and tremulane-type scaffolds (1-7) were produced byP. orientoasiaticus, whereas a drimane-type sesquiterpene (8) wasproduced byX. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds1-7exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 mu MN