Bio-sustainable production of natural medicines from Vitex

Informazioni relative al progetto

MediVAC

ID dell’accordo di sovvenzione: 658677

DOI

10.3030/658677

Progetto chiuso

Data della firma CE 4 Marzo 2015

Data di avvio 1 Maggio 2015

Data di completamento 30 Aprile 2017

Finanziato da

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Costo totale

€ 200 194,80

Contributo UE

€ 200 194,80

Coordinato da

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - MediVAC (Bio-sustainable production of natural medicines from Vitex)

Periodo di rendicontazione: 2015-05-01 al 2017-04-30

Sintesi del contesto e degli obiettivi generali del progetto

Vitex agnus-castus is a medicinal plant clinically shown to be an effective treatment for premenstrual syndrome. The bioactive constituents are diterpenoids that can interact with dopamine receptors in the pituitary gland. This specific activity opens up the possibility of other therapeutic applications where dopaminergic drugs are required. The major barrier to the development of V. agnus-castus diterpenoid drugs, and the further exploration of their pharmacological activity, is the lack of a source of pure compounds. MediVAC was a 24 month research project that aimed to investigate the genes involved in the biosynthesis of pharmacologically active diterpenoids in V. agnus-castus and to develop tools that would enable their production in biotechnological platforms.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

In this project state-of-the-art imaging mass spectrometry tools were used to identify diterpenoid rich tissues which were targeted for transcriptomics. Through the integration of bioinformatic, molecular biology and analytical chemistry techniques, diterpene synthases and cytochrome P450 enzyme candidates potentially involved in V. agnus-castus diterpenoid biosynthesis were identified and functionally characterised. This work resulted in a molecular toolbox of diterpenoid genes that were expressed in yeast for the production of V. agnus-castus diterpenoids. The engineered host strains hold potential for the future development of an industrial scale production platform able to produce high-purity, bioactive diterpenoids.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The impact of this project on the scientific community has been to provide new knowledge on the biosynthesis of high-value diterpenoids in a widely used medicinal plant. Through this project it could be demonstrated how specific combinations of diterpene synthases from V. agnus-castus can form the large majority of diterpenoid backbones found in this species. In addition, the P450 enzymes described in this work show novel activities that may facilitate further identification of enzymes involved in the formation of diterpenoids with therapeutic activities. The metabolite and transcriptomic resources developed as part of this project will be important additions to the growing catalogue of databases used for identifying new biosynthetic pathways towards valuable pharmaceuticals and nutraceuticals. It is envisioned that the future, wider benefits to society of this and related work will ultimately be access to new pharmaceuticals that are more affordable and more sustainably produced.

Ripening fruit of Vitex agnus-castus.