Investigations into the function of two plant sesquiterpene synthases: δ-cadinene synthase and (e)-β-farnesene synthase

Li, Amang 2011. Investigations into the function of two plant sesquiterpene synthases: δ-cadinene synthase and (e)-β-farnesene synthase. PhD Thesis, Cardiff University.

Preview

PDF - Accepted Post-Print Version Download (28MB) | Preview

Abstract

Terpenoids represent the most structurally and stereochemically diverse family of natural products with more than 55,000 terpenoid structures discovered to date from all life forms. Sesquiterpenes are a class of the terpenoid family, and their formation from farnesyl diphosphate is catalyzed by sesquiterpene synthases. This project focuses on trying to decipher the reaction mechanisms of two sesquiterpene synthases, 6-cadinene synthase from Gossypium arboreum and (2<r)- 3-farnesene synthase from Mentha x piperita and to provide a method for the generation of unnatural terpenes with potential commercial applications in both the pharmaceutical and agrochemical industries. Modifications by substitution of residues around the active site of 6-cadinene synthase did not lead to any functional divergence, indicating an unusual structural component that determines the product specificity of this enzyme. Domain-swapping experiments based on phylogenetic information suggested that the subdomain encoded by exon 4 is most likely the key structure element controlling the product specificity of this enzyme. Manipulation of the active site volume of (2T)-p-farnesene synthase by site-directed mutagenesis revealed a rigid active site cavity that is precisely defined for generating mainly acyclic products. The active site hybrid constructed by replacing the active surface of (&pound;)-p-farnesene synthase with the corresponding part from 6-cadinene synthase lost activity, suggesting the catalytic specificity of this enzyme is modulated at a distance by residues surrounding the active site, which may have a huge influence on the active site volume. Mechanistic studies utilizing a substrate analogue revealed a new reaction mechanism for (&pound;)-P-farnesene synthase. Functional approaches to explore the N-termini region of 6-cadinene synthase and (&pound;)-p-farnesene synthase provided direct evidence that suggested dual roles for this region.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Schools > Chemistry
Subjects:	Q Science > QD Chemistry
ISBN:	9781303222962
Date of First Compliant Deposit:	30 March 2016
Last Modified:	18 Apr 2026 09:33
URI:	https://orca.cardiff.ac.uk/id/eprint/55131

Actions (repository staff only)

Edit Item