Drimane-type sesquiterpenes (DTSs) are bioactive natural products found in various organisms. We review the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity. The catalytic motifs, domain functions and underlying mechanisms of the DTS synthases in constructing drimane scaffold are summarized. These discoveries present valuable opportunities for exploring DTSs biosynthesis through genome mining.

Abstract

Drimane-type sesquiterpenes (DTSs) are significant terpenoid natural products characterized by their unique C₁₅ bicyclic skeleton. They are produced by various organisms including plants, fungi, bacteria and marine organisms, and exhibit a diverse array of bioactivities. These bioactivities encompass antifeedant, anti-insecticidal, anti-bacterial, anti-fungal, anti-viral and anti-proliferative properties. Some DTSs contribute to the pungent flavor found in herb plants like water pepper, while others serve as active components responsible for the anti-cancer activities observed in medicinal mushrooms such as (−)-antrocin from Antrodia cinnamomea. Recently, DTS synthases have been identified in various organisms, biosynthesizing drimenol, drim-8-ene-11-ol and (+)-albicanol, which all possess the characteristic drimane skeleton. Interestingly, despite these enzymes producing chemical molecules with a drimane scaffold, they exhibit minimal amino acid sequence identity across different organisms. This Concept article focuses on the discovery of DTS synthases and the tailoring enzymes generating the chemical diversity of drimane natural products. We summarize and discuss their key features, including the chemical mechanisms, catalytic motifs and functional domains employed by these terpene synthases to generate DTS scaffolds.