Neofunctionalization underlies the evolutionary origin of sclareol biosynthesis in the mint family.
basic_science · Level V
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- Record sourced from PubMed, PMID 42173900.
- Also identified by DOI 10.1038/s41467-026-73637-5.
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Abstract
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.