Ancient plant-like terpene biosynthesis in corals

Area of Science:

• Marine Biology
• Biochemistry
• Natural Product Chemistry

Background:

• Octocorals are prolific sources of diverse terpenoid natural products.
• Marine sessile animals were previously thought to rely on symbiotic microbes for natural product biosynthesis.
• The biosynthetic origins of many octocoral-derived terpenoids remain largely unknown.

Purpose of the Study:

• To challenge the paradigm of microbial biosynthesis in marine invertebrates.
• To identify and characterize animal-encoded enzymes responsible for octocoral terpenoid production.
• To explore the biotechnological potential of octocoral-derived compounds for biomedical applications.

Main Methods:

• Bioinformatic analysis to identify potential terpene cyclase (TC) genes in octocoral genomes.
• Heterologous expression and biochemical characterization of 15 octocoral TC enzymes.
• X-ray crystallography to determine the structural features of coral TCs.
• Gene localization studies to investigate co-regulation with other biosynthetic genes.

Main Results:

• A novel, monophyletic lineage of animal-encoded terpene cyclases (TCs) was identified in octocorals.
• Fifteen octocoral TC enzymes were characterized, several producing precursors to known coral terpenoids (e.g., pseudopterosin, lophotoxin, eleutherobin).
• Coral TCs share structural and active site similarities with bacterial TCs, suggesting horizontal gene transfer or a common ancestor.
• The enzyme responsible for the coral-exclusive capnellane scaffold was identified.
• TC genes were found to be co-localized with genes for terpene-modifying enzymes.

Conclusions:

• Octocorals possess intrinsic biosynthetic capabilities for complex terpenoids, challenging the long-held view of microbial symbiont dominance.
• The identified octocoral TCs represent a significant discovery in animal biochemistry and natural product biosynthesis.
• This research unlocks the potential for discovering novel pharmaceuticals from octocorals through biotechnological applications.