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Cytochrome P450 engineering information


This article covers protein engineering[1] of cytochrome (CYP) P450 enzymes. P450s are involved in a range of biochemical catabolic and anabolic process.[2] Natural P450s can perform several different types of chemical reactions including hydroxylations, N,O,S-dealkylations, epoxidations, sulfoxidations, aryl-aryl couplings, ring contractions and expansions, oxidative cyclizations, alcohol/aldehyde oxidations, desaturations, nitrogen oxidations, decarboxylations, nitrations, as well as oxidative and reductive dehalogenations.[2][3] Engineering efforts often strive for 1) improved stability 2) improved activity 3) improved substrate scope 4) enabled ability to catalyze unnatural reactions.[4][5] P450 engineering is an emerging field in the areas of chemical biology and synthetic organic chemistry (chemoenzymatic).

  1. ^ Brannigan, James; Wilkinson, Anthony (December 2002). "Protein engineering 20 years on". Nature Reviews Molecular Cell Biology. 3 (12): 964–70. doi:10.1038/nrm975. PMID 12461562. S2CID 1591624.
  2. ^ a b McIntosh, John; Farwell, Christopher; Arnold, Frances (March 20, 2014). "Expanding P450 catalytic reaction space through evolution and engineering". Current Opinion in Chemical Biology. 19: 126–134. doi:10.1016/j.cbpa.2014.02.001. PMC 4008644. PMID 24658056.
  3. ^ Munro, Andrew; Girvan, Hazel; McLean, Kirsty (December 15, 2006). "Variations on a (t)heme-novel mechanisms, redox partners and catalytic functions in the cytochrome P450 superfamily". Natural Product Reports. 24 (3): 585–609. doi:10.1039/B604190F. PMID 17534532.
  4. ^ Jung, Sang; Lauchli, Ryan; Arnold, Frances (March 14, 2011). "Cytochrome P450: taming a wild type enzyme". Current Opinion in Biotechnology. 22 (6): 809–817. doi:10.1016/j.copbio.2011.02.008. PMC 3118264. PMID 21411308.
  5. ^ Fasan, Rudi (February 22, 2012). "Tuning P450 Enzymes as Oxidation Catalysts". ACS Catalysis. 2 (4): 647–666. doi:10.1021/cs300001x. S2CID 4674699.

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Cytochrome P450 engineering

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alkenes. Arene oxides are intermediates in the oxidation of arenes by cytochrome P450. For prochiral arenes (naphthalene, toluene, benzoates, benzopyrene)...

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plays the most important role, followed by CYP2B6. In addition to the cytochrome P450 system, sertraline can be oxidatively deaminated in vitro by monoamine...

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