Double Bond Geometry Controls Diterpene Synthase Catalysis
Abstract
Abstract Terpene synthases (TSs) generate extraordinary structural complexity through carbocation cascades, but the mechanistic role of the substrate’s alkene geometry in directing enzyme catalysis remains unexplored. Here, we interrogate diterpene synthase (DTS) mechanisms using a 6Z-configured geranylgeranyl diphosphate analogue ((6Z)-GGPP) as a probe. Across a diverse panel of class I DTSs, substitution of the natural substrate GGPP with (6Z)-GGPP led to profound shifts in product profiles, yielding a wide array of diterpenes that exhibit multiple previously unreported carbon skeletons. A mechanistic analysis combining isotopic labeling experiments and density functional theory (DFT) calculations reveals that the 6Z double bond reshapes carbocationic landscapes, explaining the enzymatic formation of the isolated products.
Fields of Study & Subjects
Plant biochemistry and biosynthesis
Biological Activity of Diterpenoids and Biflavonoids
Biochemical Acid Research Studies
Publication details
- Journal / source
- ACS Catalysis
- Publisher
- American Chemical Society (ACS)
- Volume
- 16
- Issue
- 9
- Pages
- 8774–8783
- Publication date
- 9 April 2026
- Language
- EN