New method for the production of the compounds with anti-cancer activity, Arglabin and Parthenolide

Wageningen University is seeking commercial partners interested in producing the anti-cancer compounds Parthenolide, Hydroxy-Parthenolide and Arglabin through microbial production platforms and/or plants expressing their biosynthesis genes.

Summary

Parthenolide and Arglabin occurs naturally in plants, such as Tanacetum parthenium (Feverfew) and Artemisia glabella (smooth Wormwood) and show strong anti-cancer activity (Guzman et. al, Blood. 2005; 105(11): 4163–4169). Dimethylaminoparthenolide is currently in phase I clinical trials and Arglabin dimethylamino adduct is a registered antitumor substance in the Republic of Kazakhstan. The lack of water-solubility and bioavailability limits so far the potential of Parthenolide as a drug.

To solubilize Parthenolide and Arglabin, extra and intensive chemical steps are needed to develop dimethylaminoparthenolide or the Arglabin derivative (Arglabin dimethylamino adduct). The lack of knowledge on the last step in the biosynthesis pathway of Parthenolide and the largely unknown biosynthesis of Arglabin blocked up to now the potential to directly produce these compounds via biotechnological production platforms, based for example on micro-organisms.

The invention

Wageningen University scientists have identified from Feverfew and Wormwood plants the key genes in the biosynthesis of Parthenolide, water-soluble Parthenolide (Hydroxy-Parthenolide) and Arglabin. When the genes are expressed in yeast and in Nicotiana benthamiana plants, both systems are able to produce de novo Parthenolide, the water-soluble Hydroxy-Parthenolide and Arglabin.

Applications

Development of genetically modified plants and/or microbial production platforms for contained, continuous and direct production of the potentially anti-cancer compounds Parthenolide - in its water-soluble form - and Arglabin.

Benefits

  • Provides biosynthesis genes for the production of Parthenolide in its water-soluble form and Arglabin
  • May simplify the production of these potential anti-cancer compounds
  • May form the basis of a continuous, efficient production process
  • Production can be optimised and improved to cut costs

Stage of development

Development phase – laboratory tested. Yeast and plants were transformed with the genes and they successfully produced the target compounds.