Neofunctionalization underlies the evolutionary origin of sclareol biosynthesis in the mint family
- Fei Dong
- Marion Verdenaud
- Gabriele Adam
- Feng-Quan Tan
- Wissame Mouloud
- Stephanie Drevensek
- Melissa Hanique
- Clement Pichot
- Fabien Marcel
- Francoise Gilard
- Bertrand Gakière
- Alexandra Launay-Avon
- Etienne Delannoy
- Benoit Join
- Johannes Panten
- Michel Dron
- Abdelhafid Bendahmane
- Adnane Boualem
2026-05-22
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.