Discovery of iridoid cyclase completes the iridoid pathway in asterids
Iridoids are specialized monoterpenes ancestral to asterid flowering plants<sup>1,2</sup> that play key roles in defence and are also essential precursors for pharmacologically important alkaloids<sup>3,4</sup>. The biosynthesis of all iridoids involves the cyclization of the reactive biosynthetic intermediate 8-oxocitronellyl enol. Here, using a variety of approaches including single-nuclei sequencing, we report the discovery of iridoid cyclases from a phylogenetically broad sample of asterid species that synthesize iridoids. We show that these enzymes catalyse formation of 7S-cis-trans and 7R-cis-cis nepetalactol, the two major iridoid stereoisomers found in plants. Our work uncovers a key missing step in the otherwise well-characterized early iridoid biosynthesis pathway in asterids. This discovery unlocks the possibility to generate previously inaccessible iridoid stereoisomers, which will enable metabolic engineering for the sustainable production of valuable iridoid and iridoid-derived compounds.
Authors
- Ron P. Dirks (ORCID: https://orcid.org/0000-0003-4698-6170)
- Adriana A. Lopes (ORCID: https://orcid.org/0000-0003-1107-2547)
- Joshua C. Wood (ORCID: https://orcid.org/0000-0002-7691-6088)
- Maite Colinas (ORCID: https://orcid.org/0000-0001-7053-2983)
- Klaus Gase (ORCID: https://orcid.org/0000-0002-8028-5645)
- Sarah E. O’Connor (ORCID: https://orcid.org/0000-0003-0356-6213)
- Anja David
- C. Robin Buell (ORCID: https://orcid.org/0000-0002-6727-4677)
- Gabriel R. Titchiner (ORCID: https://orcid.org/0000-0002-6378-9884)
- Lorenzo Caputi (ORCID: https://orcid.org/0000-0002-7783-6733)
- John P. Hamilton (ORCID: https://orcid.org/0000-0002-8682-5526)
- Ryan M. Alam (ORCID: https://orcid.org/0000-0002-0227-0771)
- Sarah Heinicke
- Jens Wurlitzer
- Clara Morweiser
- Chloée Tymen
Institutions
- Universidade de Ribeirão Preto (BR)
- University of Georgia (US)
- Max Planck Institute for Chemical Ecology (DE)
- Cancer Genomics Centre (NL)
- Applied Genetic Technologies (United States) (US)
Publication Details
- Journal
- Nature Plants
- Published
- 2025-10-03
- DOI
- https://doi.org/10.1038/s41477-025-02122-6
- Citations
- 3
- Primary Topic
- Phytochemistry and Biological Activities
- Type
- article
- Field-Weighted Citation Impact
- 5.25
Funders
- Georgia Research Alliance
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- Leibniz-Gemeinschaft