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Use of Chemical Auxiliaries to Control P450 Enzymes for Predictable Oxidations at Unactivated C-H Bonds of Substrates

  • Karine AuclairEmail author
  • Vanja Polic
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 851)

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.

Keywords

Biocatalysis Decoy molecule Fatty acid Perfluorinated carboxylic acid Carbolide Chemical auxiliary Theobromine Molecularly imprinted polymer 

Notes

Acknowledgments

Writing of this chapter and research in the area of P450 enzymes in the Auclair group have been funded by the National Science and Engineering Research Council of Canada (NSERC), the Center in Green Chemistry and Catalysis, Merck Frosst Canada Ltée, Boehringer Ingelheim Canada and AstraZeneca Canada. V.P. was supported by scholarships from the Dr. Richard H. Tomlinson Foundation, Walter C. Sumner Foundation and the Centre in Green Chemistry and Catalysis.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of ChemistryMcGill UniversityMontrealCanada

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