Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum.

Jan Rinkel,Jeroen S Dickschat

doi:10.3762/bjoc.15.75

Abstract

A newly identified bacterial (Z)-γ-bisabolene synthase was used for investigating the cyclisation mechanism of the sesquiterpene. Since the stereoinformation of both chiral putative intermediates, nerolidyl diphosphate (NPP) and the bisabolyl cation, is lost during formation of the achiral product, the intriguing question of their absolute configurations was addressed by incubating both enantiomers of NPP with the recombinant enzyme, which resolved in an exclusive cyclisation of (R)-NPP, while (S)-NPP that is non-natural to the (Z)-γ-bisabolene synthase was specifically converted into (E)-β-farnesene. A hypothetical enzyme mechanistic model that explains these observations is presented.

Highlights

Given the enormous impact of chirality within biomolecules for all forms of life, it is fascinating to see how nature is able to maintain and reproduce stereochemical information
Since the stereoinformation of both chiral putative intermediates, nerolidyl diphosphate (NPP) and the bisabolyl cation, is lost during formation of the achiral product, the intriguing question of their absolute configurations was addressed by incubating both enantiomers of NPP with the recombinant enzyme, which resolved in an exclusive cyclisation of (R)-NPP, while (S)-NPP that is non-natural to the (Z)-γ-bisabolene synthase was converted into (E)-β-farnesene
We addressed the chiral intermediates in the biosynthesis of the achiral sesquiterpene (Z)-γ-bisabolene (5) by a terpene synthases (TSs) from a soil bacterium

Summary

Introduction

Given the enormous impact of chirality within biomolecules for all forms of life, it is fascinating to see how nature is able to maintain and reproduce stereochemical information. Since the stereoinformation of both chiral putative intermediates, nerolidyl diphosphate (NPP) and the bisabolyl cation, is lost during formation of the achiral product, the intriguing question of their absolute configurations was addressed by incubating both enantiomers of NPP with the recombinant enzyme, which resolved in an exclusive cyclisation of (R)-NPP, while (S)-NPP that is non-natural to the (Z)-γ-bisabolene synthase was converted into (E)-β-farnesene.

Results

Conclusion