C. J. Schofield
University of Oxford
FROM THE CHEMISTRY OF PENICILLIN TO OXYGEN SENSING IN HUMANS
Oxygenases are involved in the biosynthesis of a range of natural products where they often catalyse synthetically impossible reactions such as occur in beta-lactam biosynthesis. Oxygenases also play important roles in the physiology of humans. In animals the response to limiting oxygen availability is mediated by the hypoxia inducible transcription factor (HIF). Both the levels and activity of HIF are regulated by its post-translational hydroxylation of conserved prolyl and asparaginyl residues. These modifications are catalysed by Fe(II) and 2-oxoglutarate dependent oxygenases which are also involved in nucleasome modifications. The talk will discuss the biochemical and structural features that enable 2OG oxygenase catalsyis in a range of biosynthetic/biological contexts. The lecture will describe evidence that post-translational hydroxylations, including N-demethylations via hydroxylation, are much more widespread that was thought and are likely involved in the regulation of all steps in protein biosynthesis in aerobic organisms.
We thank the Wellcome Trust, BBSRC and European Union for funding our research.