Cytochromes P450 as versatile biocatalysts

摘要

Cytochromes P450 are ubiquitously distributed enzymes, which were discovered about 50 years ago and which possess high complexity and display a broad field of activity. They are hemoproteins encoded by a superfamily of genes converting a broad variety of substrates and catalysing a variety of interesting chemical reactions. This enzyme family is involved in the biotransformation of drugs, the bioconversion of xenobiotics, the metabolism of chemical carcinogens, the biosynthesis of physiologically important compounds such as steroids, fatty acids, eicosanoids, fat-soluble vitamins, bile acids, the conversion of alkanes, terpenes, and aromatic compounds as well as the degradation of herbicides and insecticides. There is also a broad versatility of reactions catalysed by cytochromes P450 such as carbon hydroxylation, heteroatom oxygenation, dealkylation, epoxidation, aromatic hydroxylation, reduction, dehalogenation (Sono, M., Roach, M.P., Coulter, E.D., Dawson, J.H., 1996. Heme-containing oxygenases. Chem. Rev. 96, 2841-2888), (Werck-Reichhart, D., Feyereisen, R., 2000. Cytochromes P450: a success story. Genome Biol. 1 (REVIEWS3003)), (Bernhardt, R., 2004. Cytochrome P-450. Encyclopedia Biol. Chem. 1, 544-549), (Bernhardt, R., 2004. Optimized chimeragenesis; creating diverse P450 functions. Chem. Biol. 11, 287-288), (Guengerich, F.P., 2004. Cytochrome P450: what have we learned and what are the future issues? Drug Metab. Rev. 36, 159-197). More than 5000 different P450 genes have been cloned up to date (for details see: ). Members of the same gene family are defined as usually having >/=40% sequence identity to a P450 protein from any other family. Mammalian sequences within the same subfamily are always >55% identical. The numbers of individual P450 enzymes in different species differ significantly, showing the highest numbers observed so far in plants. The structure-function relationships of cytochromes P450 are far from being well understood and their catalytic power has so far hardly been used for biotechnological processes. Nevertheless, the set of interesting reactions being catalysed by these systems and the availability of new genetic engineering techniques allowing to heterologously express them and to improve and change their activity, stability and selectivity as well as the increasing interest of the industry in life sciences makes them promising candidates for biotechnological application in the future.