Abstract
Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.
Original language | English |
---|---|
Pages (from-to) | E4407–E4414 |
Number of pages | 8 |
Journal | Proceedings of the National Academy of Sciences of the United States of America (PNAS) |
Volume | 113 |
Issue number | 30 |
Early online date | 13 Jul 2016 |
DOIs | |
Publication status | Published - Jul 2016 |
Profiles
-
Andrew Hemmings
- School of Biological Sciences - Professor of Structural Biology
- School of Chemistry, Pharmacy and Pharmacology - Professor
- Centre for Molecular and Structural Biochemistry - Member
- Chemistry of Life Processes - Member
- Molecular Microbiology - Member
- Plant Sciences - Member
Person: Research Group Member, Research Centre Member, Academic, Teaching & Research