title: Chimeric P450 enzymes: activity of artificial redox fusions driven by different reductases for biotechnological applications.
abstract: This review covers the current state of knowledge regarding artificial fusion constructs of cytochrome P450 enzymes in which the activity of the catalytic heme is driven by reductases of different origins. Cytochromes P450 form a vast family of heme-thiolate proteins, which act as monooxygenases by activating molecular oxygen, resulting in the insertion of one atom into an organic substrate with the concomitant reduction of the other to water. The reducing equivalents are usually supplied by nicotinamide adenine dinucleotide or nicotinamide adenine dinucleotide phosphate and are transferred in two consecutive steps via the redox partner(s). These include reductases containing flavin mononucleotide and/or flavin adenine dinucleotide and/or Fe-S clusters in different combinations depending on the P450 system. These enzymes catalyze extremely diverse reactions, including regio- and stereospecific oxidations of a large range of substrates in addition to many drugs and xenobiotics, as well as biosynthesis of physiologically important compounds such as various steroids, vitamins, and lipids. Because of their ability to catalyze such a vast range of reactions, they have become the focus of biotechnological interest, but their dependence on the reductase partner has remained one of the challenging limitations for full exploration of their synthetic potential. To address the latter limitation, many researchers have reconstituted functional P450 enzymes by fusion with different reductase proteins; this review will cover their findings.
authors.affiliation: Department of Life Sciences and Systems Biology, University of Torino, Torino, Torino, Italy.
authors.forename: Sheila J
authors.initials: SJ
authors.lastname: Sadeghi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gilardi
mesh_terms: D001709:Biotechnology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases