Biosynthesis of 17-Carbon Terpenoids in Bacteria

Terpenoids are the largest group of specialized metabolites with broad biological activities and applications. While terpenoid biosynthesis was long thought to generate only backbones with multiples of five carbons, the discovery of bacterial 16-carbon terpenoids challenged this view. Here, we expand our understanding of terpenoid biosynthesis by identifying and characterizing 17-carbon terpenoids. Through genome mining and functional analysis, we reveal a diverse array of structurally complex C 17 terpenoids synthesized via a conserved pathway. Two methyltransferases successively modify farnesyl diphosphate into a C 17 diphosphate precursor, which terpene synthases convert into distinct C 17 scaffolds. Phylogenetic analysis shows that C 17 terpene synthases evolved multiple times from C 16 -associated enzymes, while the latter can also generate C 17 terpenoids. These findings establish C 16 synthases as an evolutionary reservoir for C 17 biosynthesis, broadening our understanding of terpenoid diversity and evolution, while paving the way for the biological, chemical, and biotechnological exploration of this new terpenoid class.