title: Use of chemical auxiliaries to control p450 enzymes for predictable oxidations at unactivated C-h bonds of substrates.
abstract: Cytochrome P450 enzymes (P450s) have the ability to oxidize unactivated C-H bonds of substrates with remarkable regio- and stereoselectivity. Comparable selectivity for chemical oxidizing agents is typically difficult to achieve. Hence, there is an interest in exploiting P450s as potential biocatalysts. Despite their impressive attributes, the current use of P450s as biocatalysts is limited. While bacterial P450 enzymes typically show higher activity, they tend to be highly selective for one or a few substrates. On the other hand, mammalian P450s, especially the drug-metabolizing enzymes, display astonishing substrate promiscuity. However, product prediction continues to be challenging. This review discusses the use of small molecules for controlling P450 substrate specificity and product selectivity. The focus will be on two approaches in the area: (1) the use of decoy molecules, and (2) the application of substrate engineering to control oxidation by the enzyme.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A0B8, Canada, karine.auclair@mcgill.ca.
authors.forename: Karine
authors.initials: K
authors.lastname: Auclair
authors.forename: Vanja
authors.initials: V
authors.lastname: Polic
mesh_terms: D000818:Animals; D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D003577:Cytochrome P-450 Enzyme System