Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA.
School of Chemical Sciences, University of Auckland, Auckland, New Zealand.
Nat Chem Biol. 2022 Jun;18(6):664-669. doi: 10.1038/s41589-022-01026-2. Epub 2022 May 23.
Octocorals are major contributors of terpenoid chemical diversity in the ocean. Natural products from other sessile marine animals are primarily biosynthesized by symbiotic microbes rather than by the host. Here, we challenge this long-standing paradigm by describing a monophyletic lineage of animal-encoded terpene cyclases (TCs) ubiquitous in octocorals. We characterized 15 TC enzymes from nine genera, several of which produce precursors of iconic coral-specific terpenoids, such as pseudopterosin, lophotoxin and eleutherobin. X-ray crystallography revealed that coral TCs share conserved active site residues and structural features with bacterial TCs. The identification of coral TCs enabled the targeted identification of the enzyme that constructs the coral-exclusive capnellane scaffold. Several TC genes are colocalized with genes that encode enzymes known to modify terpenes. This work presents an example of biosynthetic capacity in the kingdom Animalia that rivals the chemical complexity generated by plants, unlocking the biotechnological potential of octocorals for biomedical applications.
八放珊瑚是海洋中萜类化合物多样性的主要贡献者。其他固着海洋动物的天然产物主要是由共生微生物而不是宿主生物生物合成的。在这里，我们通过描述八放珊瑚中普遍存在的单系动物编码萜烯环化酶（TCs）家族来挑战这一长期存在的范式。我们从九个属中鉴定了 15 种 TC 酶，其中几种产生标志性珊瑚特有的萜类化合物的前体，如假珊瑚素、石珊瑚毒素和 eleutherobin。X 射线晶体学揭示了珊瑚 TCs 与细菌 TCs 共享保守的活性位点残基和结构特征。珊瑚 TCs 的鉴定使我们能够有针对性地鉴定构建珊瑚特有的帽烷支架的酶。一些 TC 基因与已知修饰萜类化合物的酶的基因共定位。这项工作展示了动物王国中生物合成能力的一个例子，可与植物产生的化学复杂性相媲美，为八放珊瑚在生物医学应用中的生物技术潜力开辟了道路。
