Centre for Cytochrome P450 Biodiversity
Part of the Microbes and Immunity research theme at Swansea University Medical School and led by Professor Steven Kelly, Professor Diane Kelly and Professor David Lamb, this research group is investigating cytochrome P450 systems of bacteria, fungi and animals. The P450 gene/enzyme system is extremely diverse, reflecting the central role it plays in xenobiotic metabolism and detoxification of diverse organic chemicals in the biosphere. As the enzymes also participate in important biosynthetic reactions such as sterol and steroid biosynthesis, inhibitors have been developed as commercially important drugs, including the azole antifungal agents, anti-protozoal therapies and the aromatase inhibiting breast cancer drugs. Other P450s may represent new targets while P450s are also involved in the biosynthesis of many of the natural products used in medicine today (e.g. erythromycin, vincristine, taxol).
The work of this group includes studies on the molecular genetics and biochemistry of these systems. It is interdisciplinary in its approach and includes medical microbiology and mycology, microbial genetics and biotechnology, toxicology, biocatalysis, molecular biology, transcriptomics, proteomics, metabolomics and structural biology. A close collaboration exists between the centre and Dr Jonathan Mullins on protein structure modelling using his commercialised multiple template homology modelling pipeline.
The Centre for Cytochrome P450 Biodiversity is always reviewing its interests, taking into account developments in post-genomic science. An ever-increasing number of cytochrome P450 genes (one per cent of a genome in some cases) are being uncovered by the DNA sequencing projects of diverse organisms and the genes generally have no known biological role. Identifying these functions in a systematic way using post-genomic technologies and bioinformatics is a challenge for the future. This will create new opportunities for basic and applied studies, besides the greater appreciation of the biology of this super family of unique proteins involving secondary metabolism, pharmacology, toxicology and biotechnology. New drugs, drug resistance and individualised responses to therapy and xenobiotic exposure are all covered in this area.