Identification of iridoid synthases from Nepeta species: Iridoid cyclization does not determine nepetalactone stereochemistry

Nathaniel H. Sherden, Benjamin Lichman, Lorenzo Caputi, Dongyan Zhao, Mohamed O. Kamileen, C. Robin Buell, Sarah E. O'Connor

Research output: Research - peer-reviewArticle

Abstract

Nepetalactones are iridoid monoterpenes with a broad range of biological activities produced by plants in the Nepeta genus. However, none of the genes for nepetalactone biosynthesis have been discovered. Here we report the transcriptomes of two Nepeta species, each with distinctive profiles of nepetalactone stereoisomers. As a starting point for investigation of nepetalactone biosynthesis in Nepeta, these transcriptomes were used to identify candidate genes for iridoid synthase homologs, an enzyme that has been shown to form the core iridoid skeleton in several iridoid producing plant species. Iridoid synthase homologs identified from the transcriptomes were cloned, heterologously expressed, and then assayed with the 8-oxogeranial substrate. These experiments revealed that catalytically active iridoid synthase enzymes are present in Nepeta, though there are unusual mutations in key active site residues. Nevertheless, these enzymes exhibit similar catalytic activity and product profile compared to previously reported iridoid synthases from other plants. Notably, four nepetalactone stereoisomers with differing stereochemistry at the 4α and 7α positions – which are generated during the iridoid synthase reaction – are observed at different ratios in various Nepeta species. This work strongly suggests that the variable stereochemistry at these 4α and 7α positions of nepetalactone diastereomers is established further downstream in the iridoid pathway in Nepeta. Overall, this work provides a gateway into the biosynthesis of nepetalactones in Nepeta.

LanguageEnglish (US)
Pages48-56
Number of pages9
JournalPhytochemistry
Volume145
DOIs
StatePublished - Jan 1 2018

Profile

Stereochemistry
Cyclization
nepetalactone
Nepeta
stereochemistry
Biosynthesis
Enzymes
Transcriptome
transcriptome
biosynthesis
enzymes
Stereoisomerism
Genes
stereoisomers
genes
Monoterpenes
Bioactivity
Catalyst activity
Substrates
Experiments

Keywords

  • Iridoid
  • Natural product biosynthesis
  • Short chain alcohol dehydrogenase
  • Terpenoid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Plant Science
  • Horticulture

Cite this

Identification of iridoid synthases from Nepeta species : Iridoid cyclization does not determine nepetalactone stereochemistry. / Sherden, Nathaniel H.; Lichman, Benjamin; Caputi, Lorenzo; Zhao, Dongyan; Kamileen, Mohamed O.; Buell, C. Robin; O'Connor, Sarah E.

In: Phytochemistry, Vol. 145, 01.01.2018, p. 48-56.

Research output: Research - peer-reviewArticle

Sherden, Nathaniel H. ; Lichman, Benjamin ; Caputi, Lorenzo ; Zhao, Dongyan ; Kamileen, Mohamed O. ; Buell, C. Robin ; O'Connor, Sarah E./ Identification of iridoid synthases from Nepeta species : Iridoid cyclization does not determine nepetalactone stereochemistry. In: Phytochemistry. 2018 ; Vol. 145. pp. 48-56
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