Research groups

Structure function and engineering of polyketide synthases

Around two thirds of all drugs in current clinical use are derived from or based upon molecules isolated from natural sources. This constitutes a multi-billion pound global market comprising antibiotics, antifungals, antiparasitics and anticancer agents. 

We are principally interested in natural products synthesised by the polyketide and related non-ribosomal peptide pathways. The group employs a range of structural (X-ray crystallography, cryo-electron microscopy, NMR and solution scattering) and functional (enzyme kinetics, spectroscopy, etc.) methods to deconvolute, at the molecular level, the catalytic mechanisms of the individual component enzymes from selected synthetic pathways. These investigations form the basis of protein engineering approaches, where we seek to manipulate pathway enzymes to yield novel derivative products with improved therapeutic activities.

Current areas of major interest in the group are:

• hybrid polyketide/non-ribosomal peptide antibiotics and anticancer drugs.
• polyketide based cholesterol lowering agents.