Protein engineering of cytochromes P-450

The cytochromes P-450 are an immensely important superfamily of heme-contai ning enzymes. They catalyze the monooxygenation of an enormous range of sub strates. In bacteria, cytochromes P-450 are known to catalyze the hydroxyla tion of environmentally significant substrates such as camphor, phenolic co mpounds and many herbicides. In eukaryotes, these enzymes perform key roles ill the synthesis and interconversion of steroids, while in mammals hepati c cytochromes P-450 are vital for the detoxification of many drugs. As such , the cytochromes P-450 are of considerable interest in medicine and biotec hnology and are obvious targets for protein engineering. The purpose of thi s article is to illustrate the ways in which protein engineering has been u sed to investigate and modify the properties of cytochromes P-450. Illustra tive examples include: the manipulation of substrate selectivity and regios pecificity, the alteration of membrane binding properties, and probing the route of electron transfer. (C) 2000 Elsevier Science B.V. All rights reser ved.