Widespread biosynthesis of 16-carbon terpenoids in bacteria.

Terpenoids are the most diverse group of specialized metabolites with numerous applications. Their biosynthesis is based on the five-carbon isoprene building block and, as a result, almost all terpenoids isolated to date are based on backbones that contain multiples of five carbon atoms. Intrigued by the discovery of an unusual bacterial terpenoid with a 16-carbon skeleton, here we investigate whether the biosynthesis of 16-carbon terpenoids is more widespread than this single example. We mine bacterial genomic information and identify potential C 16 biosynthetic clusters in more than 700 sequenced genomes. We study selected clusters using a yeast synthetic biology platform and reveal that the encoded synthases produce at least 47 different noncanonical terpenoids. By thorough chemical analysis, we explain the structures of 13 C 16 metabolites, most of which possess intricate highly strained bi- and tricyclic backbones. Our results unveil the existence of an extensive class of terpenoids in bacteria.