pubs.acs.org
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.
