Molecular evolution of P450 superfamily and P450‐containing monooxygenase systems

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Abstract
This paper reviews the classification of the P450 superfamily which is mainly based on sequence homology. The widely accepted classification by Nebert et al. [(1991) DNA Cell Biol. 10, 1‐14] as well as the results of a ‘two‐step’ multiple sequence alignment technique show that the molecular evolution of P450s, in contrast to that of many protein families, does not follow phylogeny. The data suggest that during the evolution of P450s, gene duplications and gene fusions, horizontal gene transfer and intron loss events have occurred. ‘Weak’ and ‘strong’ hierarchies in the clustering of P450 sequences were revealed. A novel evolutionary tree of the P450 superfamily has been constructed using a multiple alignment of consensus sequences. The simple classification of known P450‐containing monooxygenase systems into three‐, two‐ and one‐component systems is further discussed. Particularly, the multidomain enzyme, nitric oxide synthase (NOS), should be classified as an example of a eukaryotic one‐component P450 system since its N‐terminal (haem) domain exhibits similarity with microsomal P450s.