軟体サンゴのバイオ医療応用の可能性を解明(Study Unlocks Soft Corals’ Biomedical Potential)

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2025-06-13 カリフォルニア大学サンディエゴ校

カリフォルニア大学サンディエゴ校の研究チームは、軟質サンゴ(オクトコーラル)が生産する抗がん・抗炎症作用を持つジテルペノイドの遺伝子クラスターを解明しました。従来は自然由来のジテルペノイドの入手が困難でしたが、今回の研究で5種類のサンゴのゲノムを解析し、合成に関わる遺伝子群を特定。これらを酵母や細菌に組み込むことで、実験室での大量生産が可能であることを実証しました。環境負荷をかけずに医薬品原料を安定供給できる新技術として、今後の創薬研究に大きな貢献が期待されます。

<関連情報>

メタゾアンに広く存在する代謝遺伝子クラスター・ファミリー A widespread metabolic gene cluster family in metazoans

Natalie E. Grayson,Paul D. Scesa,Malia L. Moore,Jean-Baptiste Ledoux,Jessica Gomez-Garrido,Tyler Alioto,Todd P. Michael,Immo Burkhardt,Eric W. Schmidt & Bradley S. Moore
Nature Chemical Biology  Published:13 June 2025
DOI:https://doi.org/10.1038/s41589-025-01927-y

軟体サンゴのバイオ医療応用の可能性を解明(Study Unlocks Soft Corals’ Biomedical Potential)

Abstract

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.

 

サンゴにおける古代植物的テルペン生合成 Ancient plant-like terpene biosynthesis in corals

Immo Burkhardt,Tristan de Rond,Percival Yang-Ting Chen & Bradley S. Moore
Nature Chemical biology  Published:23 May 2022
DOI:https://doi.org/10.1038/s41589-022-01026-2

Abstract

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.

生物化学工学
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