Unearthing a sesterterpene biosynthetic repertoire in the Brassicaceae through genome mining reveals convergent evolution

Significance Sesterterpenoids are a rare terpene class with largely unexplored chemical diversity and bioactivities, representing a potential new drug source. Sesterterpene synthases catalyze the first committed biosynthesis step and shape sesterterpene structural diversity. Here, using a customized algorithm for systematically surveying plant genomes, we unearth a sesterterpene synthase gene repertoire in the Brassicaceae that synthesizes fungal-type sesterterpenes with diverse scaffolds, thus fueling the drug-discovery pipeline. Mechanistic studies shed light on the origin of structural diversification and offer insights for expanding nature’s diversity by protein engineering. Our work also supports the concept of convergent evolution in natural product biosynthesis.