Sesquiterpene cyclases catalyze the conversion of farnesyl diphosphate, a linear compound, into a dizzying array of molecular structures including monocyclic, bicyclic, tricyclic, and even tetracyclic products. These products include both sesquiterpene hydrocarbons and sesquiterpenoids containing heteroatoms (typically oxygen). The details of the chemical mechanisms catalyzed by these enzymes, including stereochemical requirements, are preserved in the molecular structures of their products. Using computational chemistry methods, models for the chemical mechanisms by which these enzymes convert farnesyl diphosphate into a range of products can be elucidated. Patchoulol synthase isolated from Pogostemon cablin (patchouli), the natural source of patchouli oil (a popular fragrance), converts farnesyl diphosphate into patchouli alcohol (a tricyclic sesquiterpenoid) plus a range of bi-, tri-, and tetra-cyclic sesquiterpene hydrocarbons. Among these products is δ-guaiene, a rare sesquiterpene that contains a bicyclo[5.3.0]decane framework improbably derived directly from transannular ring closure of a putative ten-membered ring intermediate. Rather, the mechanism proposed herein suggests the bicyclo[5.3.0]decane framework leading to delta-guaiene may emerge from "popping the lid off” of a tricyclic intermediate identified along the pathway leading toward patchouli alcohol. In summary, this mechanism explains the generation of patchouli oil as well as δ-guaiene and other products of this enzyme with stereochemical precision. Intriguingly, this mechanism also implies the nature of the evolutionary relationship between the well-characterized patchoulol synthase from Pogostemon cablin and the less-well characterized δ-guaiene synthase isoforms isolated from Aquilaria crassna (agarwood).

Popping the lid off: Rare bicyclic sesquiterpene may emerge from a tricyclic intermediate

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.