期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 22, 期 20, 页码 5547-5554出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.06.034
关键词
Anchoring molecule; Biocatalysis; Chemical auxiliary; Decoy molecule; Directing group; Fatty acid; Molecularly imprinted polymer; Perfluorinated carboxylic acid
资金
- National Science and Engineering Research Council of Canada (NSERC)
- Center in Green Chemistry and Catalysis
- Merck Frosst Canada Ltee
- Boehringer Ingelheim Canada
- AstraZeneca Canada
- Dr. Richard H. Tomlinson Foundation
- Walter C. Sumner Foundation
- Centre in Green Chemistry and Catalysis
P450 enzymes (P450s) are well known for their ability to oxidize unactivated C-H 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. (C) 2014 Elsevier Ltd. All rights reserved.
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