A widespread metabolic gene cluster family in metazoans.

Octocorals are metazoans that prolifically produce terpenoid natural products, rivaling the chemical diversity of plants and microbes. We recently established that these cnidarians uniformly express terpene cyclases and that their encoding genes often reside within putative biosynthetic gene clusters (BGCs). Here we report the discovery and characterization of a widespread gene cluster family for briarane diterpenoid biosynthesis. We sequence five genomes from evolutionarily distinct families of briarane-producing octocorals, revealing a conserved five-gene cluster. Expressing these genes in heterologous hosts, we reconstitute the biosynthesis of cembrene B γ-lactone, an established molecule that contains the lactone structural feature distinctive of briarane diterpenoids. The discovery of the genomic basis of briarane biosynthesis establishes that animals also use gene cluster families to produce specialized metabolites. Furthermore, the presence of BGCs in octocorals proves that the formation and maintenance of BGCs related to specialized metabolite biosynthesis is a more widespread phenomenon than previously realized.