Antiviral Chlorinated Drimane Meroterpenoids from the Fungus Talaromyces pinophilusLD-7 and Their Biosynthetic Pathway

Ten new drimane meroterpenoids talarines A–J (1–10), along with six known analogues (11–16), were isolated from desert soil-derived fungus Talaromyces pinophilusLD-7. Their 2D structures were elucidated by comprehensive interpretation of NMR and HRESIMS data. Electronic circular dichroism calculation was used to establish their absolute configurations. Compounds 2, 10, and 11showed antiviral activities toward vesicular stomatitis virus with IC50values of 18, 15, and 23 nM, respectively. The structure-bioactivity relationship indicated that chlorine substitution at C-5 contributed greatly to their antiviral activities. Finally, we identified a new halogenase outside the biosynthetic gene cluster, which was responsible for C-5 halogenation of the precursor isocoumarin 17as a tailoring step in chlorinated meroterpenoids assembly.