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:
Alice Robson, Marisa Till, Asha Nair, Matthew Byrne.
Cuskin F, Solovyova AS, Lewis RJ, Race PR. (2011) Crystallisation and preliminary X-ray analysis of the bacillaene synthase trans-acting acyltransferase PksC. Acta Crystallographica Section F: Structural Biology and Crystallization Communications. 67(4): 464-466.
Solovyova AS, Pointon JA, Race PR, Kehoe MA, Banfield MJ. (2010) Solution structure of the major (Spy0128) and minor (Spy0125 and Spy0130) pili subunits from Streptococcus pyogenes. European Biophysical Journal. 39(3): 469-480.
Crow A, Race PR, Jubelin G, Varela Chavez C, Escoubas JM, Oswald E, Banfield MJ. (2009) Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei. PLOS ONE. 4(5): e5582.
Race PR, Bentley ML, Melvin JA, Crow A, Hughes RK, Smith WD, Sessions RB, Kehoe M, McCafferty DG, Banfield MJ. (2009) Crystal structure of Streptococcus pyogenes sortase A: implications for sortase mechanism. Journal of Biological Chemistry. 284(11): 6924-6933.