Fungi are famous for producing a wide range of different metabolites, many of which have been exploited for pharmaceutical applications. Recent research is in the following areas:
Pleuromutilin is a diterpene antibiotic produced by the basidiomycete Clitopilus passeckerianus. We have already established the necessary tools for genetic manipulation of this fungus. Current research projects in on this fungus include analysis of gene expression during antibiotic fermentation and genetic characterisation of the pleuromutilin biosynthesis pathway. These are with the aim of engineering the fungus to produce more product, or to alter the range of products made so that new derivatives are easier to make.
Spin-offs of this research include techniques to investigate the genetic basis of other drugs made by a wide range of different mushrooms.[ref]
Polyketides in fungi are made multifunctional enzymes that are iterative – meaning that each goes through repeated incorporation and subsequent varying degrees of reduction of acetate, resulting in production of a wide range of different compounds. Our research aims to understand how these enzymes are programmed – so that the number of rounds of extension and the degree of reduction can be set to produce new compounds. This is of value because many existing pharmaceuticals are polyketides and new compounds in this class could be valuable leads for drug discovery. This research is in close collaboration with Colin Lazarus and Profs Cox and Simpson (School of Chemistry).[ref]
Non-ribosomal peptides are short peptides made by an enzyme rather than directly encoded by a specific mRNA. The best characterised of these is the Aminoadipyl-cysteinyl valine tripeptide precursor of penicillin but many aothers are also of economic interest. The natural diversity amongst such genes and their abundance in fungi make s them of interest as potential pharmaceuticals, as iron-uptake systems, or as metabolites useful in the disease of various hosts.[ref]