Sustainable Production of Thapsigargin using Light

Welcome to the homepage of SPOTLight, which is an acronym for Sustainable Production of Thapsigargin using Light.

A number of natural products like taxol, artemisinin, vincristine, and vinblastine are important drugs or precursors of drugs. The demand for some of these compounds exceeds the supply available from their natural source.  Currently, attempts are being made to meet this demand through the metabolic engineering of microorganisms.

The goal of the present project is to develop a metabolically engineered moss strain as a sustainable production platform for plant products. Production of thapsigargin has been chosen as a pilot project. Thapsigargin is the major active compound in the umbelliferous Mediterranean plant Thapsia garganica L. The agent is a potent cytotoxin, the toxicity of which can be related to its ability to inhibit the intracellular Ca²⁺ pump sitting on the membranes of the sarco- or endoplasmic reticulum (the SERCA pump). A prodrug of thapsigargin that is targeted towards cancer cells is now undergoing clinical trials for the treatment of breast, prostate, kidney, and bladder cancer. A positive outcome of these trials will create a significant demand for thapsigargin. This project is focused on meeting this demand by developing a sustainable platform for the supply of thapsigargin. The methods developed for production of thapsigargin is expected also to be applicable for production of other plant products.

The topic of the present project is highly interdisciplinary involving groups focused on gene discovery and characterization, metabolic engineering, expression of enzymes, isolation of secondary metabolites, production of natural products by synthesis, and characterization of the interaction between natural products and SERCA.

The research groups involved in the project are located at the

Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen

Department of Plant Biology and Biotechnology, Faculty of Life Sciences, University of Copenhagen

PUMPKIN, Departments of Molecular Biology and Physiology and Biophysics, University of Aarhus

The project is monitored by an advisory board consisting of

Fredrik Björling, Head of Department, Department of Medicinal Chemistry, Faculty of Pharmacy, University of Copenhagen

Birger Lindberg Møller, Professor, Department of Plant Biology and Biotechnology, Faculty of Life Sciences, University of Copenhagen

Craig Dionne, CEO, GenSpera, San Antonio, Texas, USA

Per Kudsk, Head of Research, Forskningscenter Flakkebjerg, University of Aarhus

Thank you for visiting our homepage

S. Brøgger Christensen

The project is funded by a grant from the Danish Research Council for Strategic Research and co financed by GenSpera..