A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Salmon, Melissa, Thimmappa, Ramesha B., Minto, Robert E., Melton, Rachel E., Hughes, Richard K., O'Maille, Paul E., Hemmings, Andrew M. ORCID: https://orcid.org/0000-0003-3053-3134 and Osbourn, Anne (2016) A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 113 (30). E4407–E4414. ISSN 1091-6490

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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.

Item Type: Article
Additional Information: This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1605509113/-/DCSupplemental. Freely available online through the PNAS open access option.
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Science > School of Chemistry
UEA Research Groups: Faculty of Science > Research Groups > Molecular Microbiology
Faculty of Science > Research Groups > Plant Sciences
Faculty of Science > Research Groups > Chemistry of Life Processes
Faculty of Science > Research Centres > Centre for Molecular and Structural Biochemistry
Depositing User: Pure Connector
Date Deposited: 24 Sep 2016 00:05
Last Modified: 22 Oct 2022 01:20
URI: https://ueaeprints.uea.ac.uk/id/eprint/59806
DOI: 10.1073/pnas.1605509113


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