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Monooxygenase, Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450 pp 209–228Cite as

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

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Part of the book series: Advances in Experimental Medicine and Biology ((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.

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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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  1. Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, H3A0B8, Canada

    Karine Auclair & Vanja Polic

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  1. Karine Auclair
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  2. Vanja Polic
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Correspondence to Karine Auclair .

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  1. Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada

    Eugene G. Hrycay

  2. Fac. of Pharmaceutical Sciences, The University of British Columbia , Vancouver, British Columbia, Canada

    Stelvio M. Bandiera

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Auclair, K., Polic, V. (2015). Use of Chemical Auxiliaries to Control P450 Enzymes for Predictable Oxidations at Unactivated C-H Bonds of Substrates. In: Hrycay, E., Bandiera, S. (eds) Monooxygenase, Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450. Advances in Experimental Medicine and Biology, vol 851. Springer, Cham. https://doi.org/10.1007/978-3-319-16009-2_8

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