Diverged Plant Terpene Synthases Reroute the Carbocation Cyclization Path towards the Formation of Unprecedented 6/11/5 and 6/6/7/5 Sesterterpene Scaffolds

Angew Chem Int Ed Engl. 2018 Jan 26;57(5):1291-1295. doi: 10.1002/anie.201711444. Epub 2017 Dec 28.

Abstract

Sesterterpenoids are a relatively rare class of plant terpenes. Sesterterpene synthase (STS)-mediated cyclization of the linear C25 isoprenoid precursor geranylfarnesyl diphosphate (GFPP) defines sesterterpene scaffolds. So far only a very limited number of STSs have been characterized. The discovery of three new plant STSs is reported that produce a suite of sesterterpenes with unprecedented 6/11/5 and 6/6/7/5 fused ring systems when transiently co-expressed with a GFPP synthase in Nicotiana benthamiana. Structural elucidation, feeding experiments, and quantum chemical calculations suggest that these STSs catalyze an unusual cyclization path involving reprotonation, intramolecular 1,6 proton transfer, and concerted but asynchronous bicyclization events. The cyclization is diverted from those catalyzed by the characterized plant STSs by forming unified 15/5 bicyclic sesterterpene intermediates. Mutagenesis further revealed a conserved amino acid residue implicated in reprotonation.

Keywords: cyclization; natural products; quantum chemical calculations; sesterterpene biosynthesis; terpene synthases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / classification
  • Alkyl and Aryl Transferases / metabolism*
  • Cations / chemistry
  • Cyclization
  • Gas Chromatography-Mass Spectrometry
  • Phylogeny
  • Plant Leaves / enzymology
  • Plant Leaves / metabolism
  • Plant Proteins / classification
  • Plant Proteins / metabolism*
  • Quantum Theory
  • Sesterterpenes / chemistry*
  • Sesterterpenes / metabolism
  • Tobacco / enzymology
  • Tobacco / metabolism

Substances

  • Cations
  • Plant Proteins
  • Sesterterpenes
  • Alkyl and Aryl Transferases
  • terpene synthase