Structure, Mechanism and Function of Cytochrome P450 Enzymes

The cytochromes P450 constitute a superfamily of heme b-containing monoxygenase enzymes found in organisms from all of the domains of life. They catalyse the two-electron reduction of molecular oxygen bound to their ferrous heme iron, resulting in its scission and the introduction of a single atom of oxygen into a substrate molecule, with the remaining oxygen atom used in production of a molecule of water. The cytochromes P450 have numerous functions critical to human physiology — including key roles in steroid synthesis and in the metabolism of drugs and xenobiotics. In microbes they are increasingly recognized to be important enzymes for biotechnologically relevant transformations — for instance in the synthesis of polyketides and the oxidation of cholesterol. This chapter will focus on the structural and mechanistic properties of the cytochromes P450, including recent studies that have led to major breakthroughs in the spectroscopic characterization of the reactive iron-oxo species responsible for the substrate oxidation events. It will also consider wider aspects of cytochrome P450 catalysis, including the diverse redox partner systems used by these hemoprotein enzymes to facilitate catalysis. In addition, the biomedical relevance of various cytochromes P450 will be highlighted, and selected biotechnological applications of these enzymes reviewed. The cytochromes P450 are an important class of enzymes capable of highly regio- and stereoselective substrate oxidations that are often impossible to achieve using synthetic chemistry approaches. Their applicability for industrially relevant transformations is now well recognized and they are increasingly valued as tools in industrial biotechnology.