title: Cytochromes P450: History, Classes, Catalytic Mechanism, and Industrial Application.
abstract: Cytochromes P450, a family of heme-containing monooxygenases that catalyze a diverse range of oxidative reactions, are so-called due to their maximum absorbance at 450nm, ie, "Pigment-450nm," when bound to carbon monoxide. They have appeal both academically and commercially due to their high degree of regio- and stereoselectivity, for example, in the area of active pharmaceutical ingredient synthesis. Despite this potential, they often exhibit poor stability, low turnover numbers and typically require electron transport protein(s) for catalysis. P450 systems exist in a variety of functional domain architectures, organized into 10 classes. P450s are also divided into families, each of which is based solely on amino acid sequence homology. Their catalytic mechanism employs a very complex, multistep catalytic cycle involving a range of transient intermediates. Mutagenesis is a powerful tool for the development of improved biocatalysts and has been used extensively with the archetypal Class VIII P450, BM3, from Bacillus megaterium, but with the increasing scale of genomic sequencing, a huge resource is now available for the discovery of novel P450s.
authors: Prozomix Limited, Haltwhistle, Northumberland, United Kingdom; Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.
authors: D J
authors: DJ
authors: Cook
authors: Prozomix Limited, Haltwhistle, Northumberland, United Kingdom; Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom.
authors: J D
authors: JD
authors: Finnigan
authors: Thermo Fisher Scientific, Hemel Hempstead, Hertfordshire, United Kingdom.
authors: K
authors: K
authors: Cook
authors: Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, United Kingdom. Electronic address: gary.black@northumbria.ac.uk.
authors: G W
authors: GW
authors: Black
authors: Prozomix Limited, Haltwhistle, Northumberland, United Kingdom. Electronic address: simon.charnock@prozomix.com.
authors: S J
authors: SJ
authors: Charnock
mesh_terms: D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007221:Industry
chemical_list: D003577:Cytochrome P-450 Enzyme System
keywords: (+)-Nootkatone; 1α,25-Dihydroxyvitamin D3; APIs; CYP; Ferredoxin; Flavodoxin; Flavoprotein; Hydroxylations; P450cam; Pravastatin; Protoporphyrin IX; Uncoupling