Bio-sustainable production of natural medicines from Vitex

Project Information

MediVAC

Grant agreement ID: 658677

DOI

10.3030/658677

Project closed

EC signature date 4 March 2015

Start date 1 May 2015

End date 30 April 2017

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 200 194,80

EU contribution

€ 200 194,80

Coordinated by

KOBENHAVNS UNIVERSITET
Denmark

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

Reporting period: 2015-05-01 to 2017-04-30

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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.