Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review



  • Author: Heskes, Allison Maree

    University of Copenhagen, Denmark

  • Author: Sundram, Tamil C M

    University of Copenhagen, Denmark

  • Author: Boughton, Berin Alain

    University of Melbourne, Australia

  • Author: Jensen, Niels Bjerg

    Evolva Biotech A/S, Denmark

  • Author: Hansen, Nikolaj Lervad

    University of Copenhagen, Denmark

  • Author: Crocoll, Christoph

    University of Copenhagen, Denmark

  • Author: Cozzi, Federico

    University of Copenhagen, Denmark

  • Author: Rasmussen, Simon

    Metagenomics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Hamberger, Britta

    University of Copenhagen, Denmark

  • Author: Hamberger, Björn

    University of Copenhagen, Denmark

  • Author: Stærk, Dan

    University of Copenhagen, Denmark

  • Author: Møller, Birger Lindberg

    University of Copenhagen, Denmark

  • Author: Pateraki, Irini

    University of Copenhagen, Denmark

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Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus-castus. With the assistance of matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome-specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs), three class I diTPSs, and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus-castus. The identified CYP, VacCYP76BK1, was found to catalyse 16-hydroxylation of the diol-diterpene, peregrinol, to labd-13Z-ene-9,15,16-triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan and lactone containing diterpenoids that are present in this species.
Original languageEnglish
JournalPlant Journal
Issue number5
Pages (from-to)943-958
Number of pages16
Publication statusPublished - 2018

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License,which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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    Research areas

  • Vitex agnus-castus, Lamiaceae, MALDI-MS imaging, Bioactive diterpenoid, Cytochrome P450, Terpene synthase

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