Sustainable Production of Thapsigargin using Light (SPOTLight)

The aim of the project is to devise a regular supply of drugs mimicking plant natural products. Focus is on already marketed drugs as well as drugs in clinical and preclinical trials. The moss Physcomitrella patens will be transformed into an efficient producer of desired lead compounds, drug precursors or the final product. From the onset we will focus on production of sesquiterpene lactones, with the first target compound being thapsigargin. Future projects will remain within the class of sesquiterpene lactones because these molecules in general are pharmacological active compounds within this class.

 

Thapsigargin, the first target compound, is currently being developed into a drug for prostate cancer therapy. Cancer of the prostate forms the 2nd most common class of cancer in males in the Western world and accounts for 40,000 deaths per year in the US. We will transform Physcomitrella to produce Thapsigargin because in the future the collection of wild plants for isolation of the compound will not meet the market demand. The genes for the biosynthesis of thapsigargin will be obtained from either Thapsia garganica, T. gymnesica and T. villosa, as these species produce thapsigargin and similar sesquiterpeniods in the majority of the plant tissue and store it in the fruit capsule. Plant material has been obtained through our collaboration partners. Parts of the genome sequence will be obtained as part of this project.

 

This work will be performed in close collaborations with research groups from the Faculty of Life Sciences and the Faculty of Pharmaceutical Sciences, University of Copenhagen. External research partners are Poul Nissen, University of Aarhus; Pinerosa Avato, University of Bari; and Dae-Kyun Ro, University of Calgary.
 
The project has recently been supported by The Danish Council for Strategic Research, and previously by  The Danish Agency for Science, Technology and Innovation, Carlsbergfondet, Fonden af 1870, Kong Christian d. X’s fond.

 

The project is part of the larger SPOTLIGHT research project.
 
Links to other sources of infomation:
Han vil gøre mosplante til medicinfabrik
Lægemiddel mod prostatakræft
Prostate cancer specific derivatives of thapsigargin