UC San Diego

Octocorals are metazoans that prolifically produce terpenoid natural products, rivaling the chemical diversity of plants and microbes. However, until recently the genomic basis of this chemistry was unresolved. With the discovery of terpene cyclase (TC) genes encoded in octocoral genomes, a framework has emerged to trace the evolution of specialized metabolism in these animals. This thesis follows the genetic twists and turns that enable octocorals to generate novel chemistry and shows how functional characterization both validates genomic trends and provides mechanistic insight into enzyme evolution. Chapter 2 explores deep-sea octocorals, sequencing and profiling specimens of both major taxonomic orders collected at depths of ~1000 m. Chemical analyses revealed broad sesquiterpene diversity, while diterpenes were largely confined to five families (XBECK). Phylogenetic and functional analyses of deep-sea coral TCs, alongside mined public data sets, revealed rich sesquiterpene synthase diversity across deeply rooted clades, as well as monophyletic groups encoding isofunctional diterpene synthases that give rise to XBECK scaffolds. These results suggest that terpenoid biosynthesis diversified early in octocoral evolution, with the last common ancestor already possessing multiple functionally distinct TC genes, highlighting the power of genomics to illuminate the history of animal specialized metabolism.Chapter 3 builds on our understanding of octocoral terpene biosynthesis evolution, identifying and characterizing a widespread biosynthetic gene cluster (BGC) family responsible for briarane diterpenoid biosynthesis. High-quality genomic data from corals spanning five families, combined with functional validation of enzyme-encoding genes, this work demonstrates that the evolutionary persistence of briarane chemistry across diverse octocoral lineages stems from a conserved BGC. This finding establishes that octocorals, like plants and microbes, rely on BGCs to encode and preserve specialized metabolism. Finally, chapter 4 focuses on a single prolific species, Leptogorgia chilensis, where a phased genome revealed extensive allelic heterozygosity and TC paralog expansions. Functional assays demonstrated how subtle active-site mutations toggle product specificity, linking allelic variation and paralog diversification to lineage-specific scaffold innovation. Collectively, these findings position octocorals as powerful models for exploring the genomic foundations of animal natural product biosynthesis and underscore their potential as reservoirs of bioactive molecules.