Grayson Natalie E, Scesa Paul D, Moore Malia L, Ledoux Jean-Baptiste, Gomez-Garrido Jessica, Alioto Tyler, Michael Todd P, Burkhardt Immo, Schmidt Eric W, Moore Bradley S
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, USA.
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT, USA.
Nat Chem Biol. 2025 Jun 13. doi: 10.1038/s41589-025-01927-y.
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.
八放珊瑚是后生动物，能大量产生萜类天然产物，其化学多样性可与植物和微生物相媲美。我们最近证实，这些刺胞动物一致表达萜烯环化酶，且其编码基因通常位于假定的生物合成基因簇（BGC）内。在此，我们报告了一个广泛存在的用于海松二萜生物合成的基因簇家族的发现与特征。我们对来自产生海松二萜的八放珊瑚进化上不同家族的五个基因组进行了测序，揭示了一个保守的五基因簇。在异源宿主中表达这些基因，我们重构了半日花二烯Bγ-内酯的生物合成，该分子含有海松二萜特有的内酯结构特征。海松二萜生物合成基因组基础的发现表明，动物也利用基因簇家族来产生特殊代谢产物。此外，八放珊瑚中BGC的存在证明，与特殊代谢产物生物合成相关的BGC的形成和维持是一种比以前认识到的更为普遍的现象。
