Chris Schofield is an Organic Chemist whose research aims to link mechanistic chemistry, biology and medicine. He came to undertake DPhil work (in the Dyson Perrins Laboratory and St John’s) in 1982, supervised by Jack Baldwin on mechanistic and biosynthetic studies on penicillins and related medicines, and motivated by a desire to understand how enzymes catalyse reactions not presently possible for non-biological synthesis.
In early independent work he made contributions to mechanisms of antibiotic resistance and in defining the special qualities of β-lactam antibiotics such as the penicillins. Insight from these studies has helped to enable development of new drugs. This work also led to textbook-recognised insights into enzyme mechanisms. Anticipating that metal dependent enzymes would become clinically relevant in beta-lactam resistance, (as is now the case), he has pioneered metallo beta-lactamase inhibitors. With Peter McHugh he characterised related human enzymes which act in the repair of DNA cross-linked with anti-cancer drugs, opening new targets.
Chris Schofield’s biosynthetic work led to structures of microbial 2-oxoglutarate (2OG) oxygenases, involved in penicillin and cephalosporin biosynthesis (with Jack Baldwin and Edward Abraham). He extended this work to plants giving insights into biosynthesis of secondary metabolites and hormones, such as the gas ethylene which is important in fruit ripening. Importantly, these studies led to the prediction that 2OG oxygenases are widely distributed, including in humans. Consequently, he initiated research to define functions of human oxygenases – they are now known to have multiple roles including in lipid metabolism and epigenetics. Breakthrough work with Peter Ratcliffe defined unprecedented mechanisms by which animals respond to hypoxia, i.e. when oxygen is limiting such as at high altitude, a long-standing physiological problem. It was shown that hydroxylations – i.e. addition of oxygen atoms to proteins – play key roles in the response of animals to hypoxia and drugs modifying these processes are now approved for anaemia treatment. He continues to work on new antibiotics (via the Ineos Oxford Institute) and the functional assignment and mechanisms of enzymes of physiological importance.