Protein engineering of cytochromes P-450.
The cytochromes P-450 are an immensely important superfamily of heme-containing enzymes. They catalyze the monooxygenation of an enormous range of substrates. In bacteria, cytochromes P-450 are known to catalyze the hydroxylation of environmentally significant substrates such as camphor, phenolic compounds and many herbicides. In eukaryotes, these enzymes perform key roles in the synthesis and interconversion of steroids, while in mammals hepatic cytochromes P-450 are vital for the detoxification of many drugs. As such, the cytochromes P-450 are of considerable interest in medicine and biotechnology and are obvious targets for protein engineering. The purpose of this article is to illustrate the ways in which protein engineering has been used to investigate and modify the properties of cytochromes P-450. Illustrative examples include: the manipulation of substrate selectivity and regiospecificity, the alteration of membrane binding properties, and probing the route of electron transfer.
Miles
C S
CS
Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR, UK.
Ost
T W
TW
Noble
M A
MA
Munro
A W
AW
Chapman
S K
SK
D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites; D002384:Catalysis; D002462:Cell Membrane / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D004579:Electron Transport; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D009251:NADPH-Ferrihemoprotein Reductase; D010084:Oxidation-Reduction; D011485:Protein Binding; D015202:Protein Engineering; D013379:Substrate Specificity
D001426:Bacterial Proteins; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases