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

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Authors

  • Melissa Salmon (Lead Author)
  • Ramesh B. Thimmappa
  • Robert E. Minto
  • Rachel E. Melton
  • Richard K. Hughes
  • Paul E. O'Maille
  • Andrew M. Hemmings
  • Anne Osbourn

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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.

Details

Original languageEnglish
Pages (from-to)E4407–E4414
JournalProceedings of the National Academy of Sciences of the United States of America (PNAS)
Volume113
Issue number30
Early online date13 Jul 2016
DOIs
Publication statusPublished - Jul 2016
Peer-reviewedYes

Bibliographic note

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.

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