Project Lead(s): Katherine Ryan
Issue
The developing world faces parasitic diseases (such as leichmaniasis and malaria) with limited tools for treatment.
For-profit pharmaceutical companies rarely invest in the development of drugs for such diseases, because it is not economic to do so.
Natural products are one possible source of new pharmaceuticals.
Solution
The project team sought to develop prototype systems for the production of complex natural products in metabolically simple hosts (like E. coli).
The idea was that production systems for natural products – which include some of the most important antibiotics, antimalarials and other drugs – could be produced from microbial hosts and thereby dramatically lower production costs and, thus, the prices of drugs.
A successful example of this approach was the yeast-based production of the artemesinin precursor.
In this study, the team sought to focus on tryptophan-based natural products using the molecule indolmycin.
Tryptophan is one of the most chemically complex biological precursors and is present in a variety of important natural product molecules.
Outcome
The project did not achieve proof of concept, due to time constraints.
Tremendous progress was made in harnessing the pathway to indolmycin. First, the team elucidated the genes and enzymes involved in making indolmycin, work that was ultimately published in the Proceedings of the National Academy of Sciences (PNAS).
The team will continue working to express this pathway in E. coli.
The project obtained $100,000 from Genome BC, beginning in October 2015 for 18 additional months of research, which should allow completion of the production system, as well as the development of new derivatives for testing and development.