Exploiting the versatility of human cytochrome P450 enzymes: the promise of blue roses from biotechnology.
The cytochrome P450 (P450) enzymes involved in drug metabolism are among the most versatile biological catalysts known. A small number of discrete forms of human P450 are capable of catalyzing the monooxygenation of a practically unlimited variety of xenobiotic substrates, with each enzyme showing a more or less wide and overlapping substrate range. This versatility makes P450s ideally suited as starting materials for engineering designer catalysts for industrial applications. In the course of heterologous expression of P450s in bacteria, we observed the unexpected formation of blue pigments. Although this was initially assumed to be an artifact, subsequent work led to the discovery of a new function of P450s in intermediary metabolism and toxicology, new screens for protein engineering, and potential applications in the dye and horticulture industries.
Gillam
E M
EM
Department of Physiology and Pharmacology, School of Biomedical Sciences, The University of Queensland, St Lucia, Australia. gillam@plpk.uq.edu.au
Guengerich
F P
FP
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001709:Biotechnology / Q000379:methods* / Q000639:trends; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D007203:Indigo Carmine; D007211:Indoles / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics; D008956:Models, Chemical; D030821:Plants, Genetically Modified; D011994:Recombinant Proteins / Q000378:metabolism
D007211:Indoles; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D007203:Indigo Carmine; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; C027185:indirubin