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<p>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 <i>Salvia sclarea</i> (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 (<i>SsLPPS</i>). 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 <i>SsLPPS</i> 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.</p>

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Neofunctionalization underlies the evolutionary origin of sclareol biosynthesis in the mint family

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月22日

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  • 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

摘要

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.