Widespread biosynthesis of 16-carbon terpenoids in bacteria.

Abstract

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 C16 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 C16 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.