Cytochrome P450 and the individuality of species

Abstract

The P450 superfamily is expanding rapidly on many fronts. Arabidopsis genomic sequencing is producing about 2 to 3 novel P450s per week, with some clusters containing 9-14 genes. Bacterial genomes also carry surprises, such as the 20 P450s found in Mycobacterium tuberculosis and the 7 in Bacillus subtilis. The race to finish the human genome has already identified the majority of human P450s, some by expressed sequence tags only. The rapid discovery of new genes is being complemented by detailed analysis of our human genes to identify and characterize the complete set of human P450 polymorphisms and disease-causing mutations, one aspect of our "chemical individuality." Phylogenetic trees are included for plant, fungal, animal, and bacterial P450s. Emphasis is given to the higher order nomenclature of P450 clans, as a tool to see the larger picture of P450 evolution. Arabidopsis is the current record holder in P450 genes, with 186 named genes and a prediction of 350 in the total genome to be completed next year. The biosynthesis of cholesterol in bacteria is discussed in relation to CYP51 as a lanosterol 14 alpha-demethylase. This enzyme may have been the first eukaryotic P450.