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 C₁₇ terpenoids synthesized via a conserved pathway. Two methyltransferases successively modify farnesyl diphosphate into a C₁₇ diphosphate precursor, which terpene synthases convert into distinct C₁₇ scaffolds. Phylogenetic analysis shows that C₁₇ terpene synthases evolved multiple times from C₁₆-associated enzymes, while the latter can also generate C₁₇ terpenoids. These findings establish C₁₆ synthases as an evolutionary reservoir for C₁₇ 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.