Neofunctionalization underlies the evolutionary origin of sclareol biosynthesis in the mint family
Plant specialized metabolites play essential ecological roles, yet the mechanisms underlying their diversification remain poorly understood. Here, we investigate the biosynthesis of sclareol, a potent antifungal diterpene produced by Salvia sclarea (clary sage). A complete telomere-to-telomere genome assembly of clary sage, compared with genomes of related Lamiaceae species that do not produce sclareol, reveals a recent tandem duplication of a class II diterpene synthase gene (SsLPPS). This duplicated enzyme acquires a specific catalytic activity, synthesizing labda-13-en-8-ol diphosphate (LPP), the direct precursor of sclareol. Structural modeling and site-directed mutagenesis identify key amino acid substitutions responsible for this neofunctionalization. Integrative genome, chromatin, and transcriptome analyses show that SsLPPS and additional diterpenoid biosynthetic genes are organized in a trichome-specific, co-regulated gene cluster. Together, our findings illustrate how enzyme innovation and regulatory rewiring can give rise to unique metabolic pathways and may inform future strategies for engineering valuable plant terpenoids.
Authors
- Feng‐Quan Tan (ORCID: https://orcid.org/0000-0003-3647-864X)
- Alexandra Launay‐Avon (ORCID: https://orcid.org/0000-0002-1993-313X)
- Clement Pichot (ORCID: https://orcid.org/0000-0002-1348-1224)
- Gabriele Adam
- Bertrand Gakière (ORCID: https://orcid.org/0000-0003-0285-5160)
- Benoît Join
- Johannes Panten
- Melissa Hanique
- Adnane Boualem (ORCID: https://orcid.org/0000-0003-4428-6496)
- Stéphanie Drevensek (ORCID: https://orcid.org/0000-0002-2356-7021)
- Étienne Delannoy (ORCID: https://orcid.org/0000-0002-0866-2063)
- Fabien Marcel (ORCID: https://orcid.org/0000-0002-8134-5961)
- Abdelhafid Bendahmane (ORCID: https://orcid.org/0000-0003-3246-868X)
- Marion Verdenaud (ORCID: https://orcid.org/0000-0002-4071-0782)
- Fei Dong (ORCID: https://orcid.org/0000-0002-7969-293X)
- Michel Dron
- Francoise Gilard (ORCID: https://orcid.org/0000-0001-9314-1555)
- Wissame Mouloud
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut des Sciences des Plantes de Paris Saclay (FR)
- Symrise (Germany) (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1038/s41467-026-73637-5
- Primary Topic
- Plant biochemistry and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement