The evolution of cytochrome P450 enzymes as biocatalysts in drug discovery and development

Gillam, Elizabeth M. J. and Hayes, Martin A. (2013) The evolution of cytochrome P450 enzymes as biocatalysts in drug discovery and development. Current Topics in Medicinal Chemistry, 13 18: 2254-2280. doi:10.2174/15680266113136660158

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Author Gillam, Elizabeth M. J.
Hayes, Martin A.
Title The evolution of cytochrome P450 enzymes as biocatalysts in drug discovery and development
Journal name Current Topics in Medicinal Chemistry   Check publisher's open access policy
ISSN 1568-0266
Publication date 2013-09
Year available 2013
Sub-type Article (original research)
DOI 10.2174/15680266113136660158
Open Access Status
Volume 13
Issue 18
Start page 2254
End page 2280
Total pages 27
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2014
Language eng
Formatted abstract
Engineered biocatalysts offer the opportunity to introduce modifications into complex lead molecules and drug candidates in a chemo-, regio- and stereoselective manner that is difficult to accomplish using traditional synthetic organic chemistry. As candidate biocatalysts, the cytochrome P450 enzymes that metabolize drugs and other xenobiotics are amongst the most versatile agents known. Not only can they mediate an exceptional range of biotransformation reactions, but they act on an unparalleled diversity of substrates. However, this versatility comes at the cost of relatively poor catalytic efficiency and low rates of coupling of cofactor consumption to product formation. Directed evolution is being used to redefine the substrate specificity of P450 enzymes while at the same time improving their efficiency, thermostability and other properties. This review will outline the key successes with bacterial P450s used as biocatalysts, examine the studies done to date with mammalian forms, and assess the prospects for exploiting xenobiotic-metabolizing P450s for applications in medicinal chemistry.
Keyword Drug development,
Cytochrome P450
Directed evolution
P450 BM3
High throughput screening
Metabolite identification
Protein engineering
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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Created: Mon, 30 Sep 2013, 13:26:42 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences