title: Controlling substrate specificity and product regio- and stereo-selectivities of P450 enzymes without mutagenesis.
abstract: P450 enzymes (P450s) are well known for their ability to oxidize unactivated CH bonds with high regio- and stereoselectivity. Hence, there is emerging interest in exploiting P450s as potential biocatalysts. Although bacterial P450s typically show higher activity than their mammalian counterparts, they tend to be more substrate selective. Most drug-metabolizing P450s on the other hand, display remarkable substrate promiscuity, yet product prediction remains challenging. Protein engineering is one established strategy to overcome these issues. A less explored, yet promising alternative involves substrate engineering. This review discusses the use of small molecules for controlling the substrate specificity and product selectivity of P450s. The focus is on two approaches, one taking advantage of non-covalent decoy molecules, and the other involving covalent substrate modifications.
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada.
authors.forename: Vanja
authors.initials: V
authors.lastname: Polic
authors.affiliation: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada. Electronic address: karine.auclair@mcgill.ca.
authors.forename: Karine
authors.initials: K
authors.lastname: Auclair
mesh_terms: D055162:Biocatalysis / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D013237:Stereoisomerism; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D003577:Cytochrome P-450 Enzyme System
keywords: Anchoring molecule; Biocatalysis; Chemical auxiliary; Decoy molecule; Directing group; Fatty acid; Molecularly imprinted polymer; Perfluorinated carboxylic acid