Exploring and Exploiting the Biosynthesis of Myriocin, a Potent Fungal Metabolite

Myriocin is a fungal metabolite that has been transformed by a medicinal chemistry programme into an effective drug (Fingolimod) to combat multiple sclerosis. The development of myriocin is a rare success story, since many fungal secondary metabolites that are attractive as medical therapeutics are too complex to optimise and synthesise on an industrial scale. Myriocin has many interesting chemical features but the biosynthetic pathways and mechanism through which the fungus is resistant to its own toxin are unknown. This project will investigate myriocin biosynthesis for the first time and will include quantification of myriocin production, optimisation of genetic transformation methods, creation of a transposon mutagenesis library, extraction and analysis of fungal sphingolipids using mass spectrometry and characterisation of myriocin biosynthetic enzymes. The project is based in the Aberdeen Fungal Group, the largest mycology group in the UK, and offers the key skills necessary for any future career in microbiology and/or industrial biotechnology. The methods are applicable to a range of organisms that produce bioactive compounds of interest to medicine and biotechnology. Dr Campopiano’s chemistry team at Edinburgh will provide inter-disciplinary scope to this project. The discovery of new intermediates for therapeutic development is a potential outcome of this project.