Work

Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas

Year: 2024

Type: article

Abstract: Biosynthesis of sodorifen with a unique C 16 -bicyclo[3.2.1]octene framework requires an S -adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the sodCD genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, pcch and pcau , from Pseudomonas sp. are heterologously expressed in Escherichia coli , leading to the discovery of two C 16 terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the pcch , pcau , and sod pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C 16 -terpenoids.

Source: Cell chemical biology

DOI: 10.1016/j.chembiol.2024.09.002