Monooxygenase, peroxidase and peroxygenase properties and reaction mechanisms of cytochrome P450 enzymes

Advances in Experimental Medicine and Biology

Volumn 851, Issue , 2015, Pages 1-61

  Hrycay, Eugene G ^a   Bandiera, Stelvio M ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Compound I; CYP protein engineering; Cytochrome P450; Monooxygenase; Peroxide shunt; Peroxygenase; Reaction mechanisms

Indexed keywords

17 HYDROXYPREGNENOLONE; 5 HYDROPEROXY 6,8,11,14 ICOSATETRAENOIC ACID; ACETOHEXAMIDE; ARACHIDONIC ACID; CITRONELLOL; CYTOCHROME P450; CYTOCHROME P450 101A1; CYTOCHROME P450 107A1; CYTOCHROME P450 107AJ1; CYTOCHROME P450 119A1; CYTOCHROME P450 119A2; CYTOCHROME P450 152A1; CYTOCHROME P450 152A2; CYTOCHROME P450 152B1; CYTOCHROME P450 153A6; CYTOCHROME P450 175A1; CYTOCHROME P450 BM3; GERANIOL; HYDROGEN PEROXIDE; ICOSATETRAENOIC ACID; LAURIC ACID; LINOLENIC ACID; OXIDOREDUCTASE; PEROXIDASE; PEROXYGENASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SELENOCYSTEINE; UNCLASSIFIED DRUG; UNSPECIFIC MONOOXYGENASE; UREA; MIXED FUNCTION OXIDASE;

AGROCYBE AEGERITA; ALPHA HELIX; AMINO ACID SEQUENCE; ARCHAEON; ARTICLE; BACILLUS MEGATERIUM; BACTERIUM; BIOCATALYST; CATALYSIS; COMPLEX FORMATION; DEALKYLATION; DEBENZYLATION; DEMETHYLATION; ENZYME MECHANISM; ENZYME STRUCTURE; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; ENZYME SYNTHESIS; EPOXIDATION; EUKARYOTE; FORMYLATION; HUMAN; HYDROGEN BOND; LIFE CYCLE; LIVER MICROSOME; NONHUMAN; OXIDATION REDUCTION REACTION; OXYGENATION; PHOTOSYNTHESIS; PRIORITY JOURNAL; PROTEIN ENGINEERING; PSEUDOMONAS PUTIDA; SITE DIRECTED MUTAGENESIS; SORANGIUM CELLULOSUM; SULFOLOBUS ACIDOCALDARIUS; SULFOLOBUS TOKODAII; SULFOXIDATION; THERMUS THERMOPHILUS; VIRUS; ANIMAL; CHEMISTRY; METABOLISM;

ARCHAEA; BACTERIA (MICROORGANISMS); MAMMALIA;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MIXED FUNCTION OXYGENASES; PEROXIDASE;

EID: 84930227374     PISSN: 00652598     EISSN: 22148019     Source Type: Book Series    
DOI: 10.1007/978-3-319-16009-2_1     Document Type: Article

References (372)

1. Hrycay EG, Bandiera SM (2012) The monooxygenase, peroxidase, and peroxygenase properties of cytochrome P450. Arch Biochem Biophys 522: 71-89.
2. http://drnelson. uthsc. edu/P450. statsfile. html.
3. Lewis DFV (1996) Cytochromes P450: structure, function and mechanism. Taylor & Francis, London.
4. Lewis DFV (2001) Guide to cytochromes P450: structure and function. Taylor & Francis, London.
5. Guengerich FP (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 14: 611-650.
6. Ortiz de Montellano PR, De Voss JJ (2005) Substrate oxidation by cytochrome P450 enzymes. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 183-245.
7. Hrycay EG, Bandiera SM (2008) Cytochrome P450 enzymes. In: Gad SC (ed) Preclinical development handbook: ADME and biopharmaceutical properties. Wiley, Hoboken, pp 627-696.
8. Hrycay EG, Bandiera SM (2009) Expression, function and regulation of mouse cytochrome P450 enzymes: comparison with human cytochrome P450 enzymes. Curr Drug Metab 10: 1151-1183.
9. Hrycay EG, Bandiera SM (2010) Addendum to ref. 8(a). Curr Drug Metab 11: 560.
10. Guengerich FP (2005) Human cytochrome P450 enzymes. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 377-530.
11. Shumyantseva VV, Bulko TV, Archakov AI (2005) Electrochemical reduction of cytochrome P450 as an approach to the construction of biosensors and bioreactors. J Inorg Biochem 99: 1051-1063.
12. Perera R, Jin S, Sono M, Dawson JH (2007) Cytochrome P450-catalyzed hydroxylations and epoxidations. Met Ions Life Sci 3: 319-359.
13. Wickramasinghe RH, Villee CA (1975) Early role during chemical evolution for cytochrome P450 in oxygen detoxification. Nature 256: 509-511.
14. Lewis DFV, Sheridan G (2001) Cytochromes P450, oxygen, and evolution. Sci World 1: 151-167.
15. Kauffman SA (1986) Autocatalytic sets of proteins. J Theor Biol 119: 1-24.
16. Wächtershäuser G (1992) Groundworks for an evolutionary biochemistry: the iron-sulphur world. Prog Biophys Mol Biol 58: 85-201.
17. Davis BK (2002) Molecular evolution before the origin of species. Prog Biophys Mol Biol 79: 77-133.
18. Nelson DR, Kamataki T, Waxman DJ, Guengerich FP, Estabrook RW, Feyereisen R, Gonzalez FJ, Coon MJ, Gunsalus IC, Gotoh O, Okuda K, Nebert DW (1993) The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12: 1-51.
19. Hrycay EG, O'Brien PJ (1971) Cytochrome P-450 as a microsomal peroxidase utilizing a lipid peroxide substrate. Arch Biochem Biophys 147: 14-27.
20. Hrycay EG, O'Brien PJ (1972) Cytochrome P-450 as a microsomal peroxidase in steroid hydroperoxide reduction. Arch Biochem Biophys 153: 480-494.
21. Hrycay EG, O'Brien PJ, Van Lier JE, Kan G (1972) Pregnene 17α-hydroperoxides as possible precursors of the adrenosteroid hormones. Arch Biochem Biophys 153: 495-501.
22. Hrycay EG, O'Brien PJ (1973) Microsomal electron transport: I. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase and cytochrome P-450 as electron carriers in microsomal NADPH-peroxidase activity. Arch Biochem Biophys 157: 7-22.
23. Hrycay EG, Prough RA (1974) Reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase and cytochrome b5 as electron carriers in NADH-supported cytochrome P-450-dependent enzyme activities in liver microsomes. Arch Biochem Biophys 165: 331-339.
24. Hrycay EG, Gustafsson JÅ, Ingelman-Sundberg M, Ernster L (1975) Sodium periodate, sodium chlorite, organic hydroperoxides and H2O2 as hydroxylating agents in steroid hydroxylation reactions catalyzed by partially purified cytochrome P-450. Biochem Biophys Res Commun 66: 209-216.
25. Hrycay EG, Gustafsson JÅ, Ingelman-Sundberg M, Ernster L (1975) Sodium periodate, sodium chlorite, and organic hydroperoxides as hydroxylating agents in hepatic microsomal steroid hydroxylation reactions catalyzed by cytochrome P-450. FEBS Lett 56: 161-165.
26. Hrycay EG, Gustafsson JÅ, Ingelman-Sundberg M, Ernster L (1976) The involvement of cytochrome P-450 in hepatic microsomal steroid hydroxylation reactions supported by sodium periodate, sodium chlorite, and organic hydroperoxides. Eur J Biochem 61: 43-52.
27. Gustafsson JÅ, Hrycay EG, Ernster L (1976) Sodium periodate, sodium chlorite, and organic hydroperoxides as hydroxylating agents in steroid hydroxylation reactions catalyzed by adrenocortical microsomal and mitochondrial cytochrome P450. Arch Biochem Biophys 174: 440-453.
28. McKay CP, Hartman H (1991) Hydrogen peroxide and the evolution of oxygenic photosynthesis. Orig Life Evol Biosph 21: 157-163.
29. Samuilov VD (1997) Photosynthetic oxygen: the role of H2O2. A review. Biochem Mosc 62: 451-454.
30. Joo H, Lin Z, Arnold FH (1999) Laboratory evolution of peroxide-mediated cytochrome P450 hydroxylation. Nature 399: 670-673.
31. Koo LS, Tschirret-Guth RA, Straub WE, Moënne-Loccoz P, Loehr TM, Ortiz de Montellano PR (2000) The active site of the thermophilic CYP119 from Sulfolobus solfataricus. J Biol Chem 275: 14112-14123.
32. Rabe KS, Kiko K, Niemeyer CM (2008) Characterization of the peroxidase activity of CYP119, a thermostable P450 from Sulfolobus acidocaldarius. ChemBioChem 9: 420-425.
33. Kellner DG, Hung SC, Weiss KE, Sligar SG (2002) Kinetic characterization of compound I formation in the thermostable cytochrome P450 CYP119. J Biol Chem 277: 9641-9644.
34. Jiang Y, Sivaramakrishnan S, Hayashi T, Cohen S, Moënne-Loccoz P, Shaik S, Ortiz de Montellano PR (2009) Calculated and experimental spin state of seleno cytochrome P450. Angew Chem Int Ed 48: 7193-7195.
35. Rittle J, Green MT (2010) Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330: 933-937.
36. Hayakawa S, Matsumura H, Nakamura N, Yohda M, Ohno H (2014) Identification of the rate-limiting step of the peroxygenase reactions catalyzed by the thermophilic cytochrome P450 from Sulfolobus tokodaii strain 7. FEBS J 281: 1409-1416.
37. Gelb MH, Heimbrook DC, Mälkönen P, Sligar SG (1982) Stereochemistry and deuterium isotope effects in camphor hydroxylation by the cytochrome P450cam monooxygenase system. Biochemistry 21: 370-377.
38. Sligar SG, Shastry BS, Gunsalus IC (1977) Oxygen reactions of the P450 heme protein. In: Ullrich V, Roots I, Hildebrandt A, Estabrook RW, Conney AH (eds) Microsomes and drug oxidations. Pergamon Press, Oxford, pp 202-209.
39. White RE, Sligar SG, Coon MJ (1980) Evidence for a homolytic mechanism of peroxide oxygen-oxygen bond cleavage during substrate hydroxylation by cytochrome P-450. J Biol Chem 255: 11108-11111.
40. Sligar SG, Gelb MH, Heimbrook DC (1984) Bio-organic chemistry and cytochrome P-450-dependent catalysis. Xenobiotica 14: 63-86.
41. Li QS, Ogawa J, Schmid RD, Shimizu S (2005) Indole hydroxylation by bacterial cytochrome P450 BM-3 and modulation of activity by cumene hydroperoxide. Biosci Biotechnol Biochem 69: 293-300.
42. Shinohara A, Kamataki T, Iizuka T, Ishimura Y, Ogoshi H, Okuda K, Kato R (1987) Drug oxidation activities of horseradish peroxidase, myoglobin and cytochrome P-450CAM reconstituted with synthetic hemes. Jpn J Pharmacol 45: 107-114.
43. Cirino PC, Arnold FH (2003) A self-sufficient peroxide-driven hydroxylation biocatalyst. Angew Chem Int Ed 42: 3299-3301.
44. Otey CR, Bandara G, Lalonde J, Takahashi K, Arnold FH (2006) Preparation of human metabolites of propranolol using laboratory-evolved bacterial cytochromes P450. Biotechnol Bioeng 93: 494-499.
45. Li QS, Ogawa J, Shimizu S (2001) Critical role of the residue size at position 87 in H2O2-dependent substrate hydroxylation activity and H2O2 inactivation of cytochrome P450BM-3. Biochem Biophys Res Commun 280: 1258-1261.
46. Khan KK, He YA, He YQ, Halpert JR (2002) Site-directed mutagenesis of cytochrome P450eryF: implications for substrate oxidation, cooperativity, and topology of the active site. Chem Res Toxicol 15: 843-853.
47. Niraula NP, Kanth BK, Sohng JK, Oh TJ (2011) Hydrogen peroxide-mediated dealkylation of 7-ethoxycoumarin by cytochrome P450 (CYP107AJ1) from Streptomyces peucetius ATCC27952. Enzyme Microb Technol 48: 181-186.
48. Matsunaga I, Ueda A, Sumimoto T, Ichihara K, Ayata M, Ogura H (2001) Site-directed mutagenesis of the putative distal helix of peroxygenase cytochrome P450. Arch Biochem Biophys 394: 45-53.
49. Shoji O, Fujishiro T, Nakajima H, Kim M, Nagano S, Shiro Y, Watanabe Y (2007) Hydrogen peroxide dependent monooxygenations by tricking the substrate recognition of cytochrome P450BSβ. Angew Chem Int Ed 46: 3656-3659.
50. Girhard M, Kunigk E, Tihovsky S, Shumyantseva V, Urlacher V (2013) Light-driven biocatalysis with cytochrome P450 peroxygenases. Biotechnol Appl Biochem 60: 111-118.
51. Girhard M, Schuster S, Dietrich M, Dürre P, Urlacher VB (2007) Cytochrome P450 monooxygenase from Clostridium acetobutylicum: a new α-fatty acid hydroxylase. Biochem Biophys Res Commun 362: 114-119.
52. Matsunaga I, Yamada M, Kusunose E, Miki T, Ichihara K (1998) Further characterization of hydrogen peroxide-dependent fatty acid α-hydroxylase from Sphingomonas paucimobilis. J Biochem 124: 105-110.
53. Shoji O, Watanabe Y (2014) Peroxygenase reactions catalyzed by cytochromes P450. J Biol Inorg Chem 19: 529-539.
54. Fujishiro T, Shoji O, Kawakami N, Watanabe T, Sugimoto H, Shiro Y, Watanabe Y (2012) Chiralsubstrate-assisted stereoselective epoxidation catalyzed by H2O2-dependent cytochrome P450SPα. Chem Asian J 7: 2286-2293.
55. Rude MA, Baron TS, Brubaker S, Alibhai M, Del Cardayra SB, Schirmer A (2011) Terminal olefin (1-alkane) biosynthesis by a novel P450 fatty acid decarboxylase from Jeotgalicoccus species. Appl Environ Microbiol 77: 1718-1727.
56. Spolitak T, Funhoff EG, Ballou DP (2010) Spectroscopic studies of the oxidation of ferric CYP153A6 by peracids: insights into P450 higher oxidation states. Arch Biochem Biophys 493: 184-191.
57. Ogura H, Nishida CR, Hoch UR, Perera R, Dawson JH, Ortiz de Montellano PR (2004) EpoK, a cytochrome P450 involved in biosynthesis of the anticancer agents epothilones A and B. Substrate-mediated rescue of a P450 enzyme. Biochemistry 43: 14712-14721.
58. Goyal S, Banerjee S, Mazumdar S (2012) Oxygenation of monoenoic fatty acids by CYP175A1, an orphan cytochrome P450 from Thermus thermophilis HB27. Biochemistry 51: 7880-7890.
59. Sheng X, Horner JH, Newcomb M (2008) Spectra and kinetic studies of the compound I derivative of cytochrome P450 119. J Am Chem Soc 130: 13310-13320.
60. Wang MY, Liehr JG (1994) Identification of fatty acid hydroperoxide cofactors in the cytochrome P450-mediated oxidation of estrogens to quinone metabolites. J Biol Chem 269: 284-291.
61. Hlavica P, Künzel-Mulas U (1993) Metabolic N-oxide formation by rabbit-liver microsomal cytochrome P-4502B4: involvement of superoxide in the NADPH-dependent N-oxygenation of N, N-dimethylaniline. Biochim Biophys Acta 1158: 83-90.
62. Rahimtula AD, O'Brien PJ (1977) The role of cytochrome P-450 in the hydroperoxide-catalyzed oxidation of alcohols by rat-liver microsomes. Eur J Biochem 77: 201-208.
63. Kadlubar FF, Morton KC, Ziegler DM (1973) Microsomal-catalyzed hydroperoxide-dependent C-oxidation of amines. Biochem Biophys Res Commun 54: 1255-1261.
64. Nordblom GD, White RE, Coon MJ (1976) Studies on hydroperoxide-dependent substrate hydroxylation by purified liver microsomal cytochrome P-450. Arch Biochem Biophys 175: 524-533.
65. Renneberg R, Scheller F, Ruckpaul K, Pirrwitz J, Mohr P (1978) NADPH and H2O2-dependent reactions of cytochrome P-450LM compared with peroxidase catalysis. FEBS Lett 96: 349-353.
66. Bui PH, Hankinson O (2009) Functional characterization of human cytochrome P450 2S1 using a synthetic gene-expressed protein in Escherichia coli. Mol Pharmacol 76: 1031-1043.
67. Renneberg R, Capdevila J, Chacos N, Estabrook RW, Prough RA (1981) Hydrogen peroxidesupported oxidation of benzo[a]pyrene by rat liver microsomal fractions. Biochem Pharmacol 30: 843-848.
68. Kumar S, Liu H, Halpert JR (2006) Engineering of cytochrome P450 3A4 for enhanced peroxidemediated substrate oxidation using directed evolution and site-directed mutagenesis. Drug Metab Dispos 34: 1958-1965.
69. Guengerich FP, Vaz ADN, Raner GN, Pernecky SJ, Coon MJ (1997) Evidence for a role of a perferryloxygen complex, FeO3+, in the N-oxidation of amines by cytochrome P450 enzymes. Mol Pharmacol 51: 147-151.
70. Kumar S, Chen CS, Waxman DJ, Halpert JR (2005) Directed evolution of mammalian cytochrome P450 2B1: mutations outside of the active site enhance the metabolism of several substrates, including the anticancer prodrugs cyclophosphamide and ifosfamide. J Biol Chem 280: 19569-19575.
71. Anari MR, Josephy PD, Henry T, O'Brien PJ (1997) Hydrogen peroxide supports human and rat cytochrome P450 1A2-catalyzed 2-amino-3-methylimidazo[4, 5-f]quinoline bioactivation to mutagenic metabolites: significance of cytochrome P450 peroxygenase. Chem Res Toxicol 10: 582-588.
72. Romano MC, Straub KM, Yodis LA, Eckardt RD, Newton JF (1988) Determination of microsomal lauric acid hydroxylase activity by HPLC with flow-through radiochemical quantitation. Anal Biochem 170: 83-93.
73. Pratt JM, Ridd TI, King LJ (1995) Activation of H2O2 by P450: evidence that the hydroxylating intermediate is iron(III)-coordinated H2O2 and not the ferryl FeO3+ complex. J Chem Soc Chem Commun 22: 2297-2298.
74. Zhang Z, Li Y, Stearns RA, Ortiz de Montellano PR, Baillie TA, Tang W (2002) Cytochrome P450 3A4-mediated oxidative conversion of a cyano to an amide group in the metabolism of pinacidil. Biochemistry 41: 2712-2718.
75. Muindi JF, Young CW (1993) Lipid hydroperoxides greatly increase the rate of oxidative catabolism of all-trans-retinoic acid by human cell culture microsomes genetically enriched in specified cytochrome P-450 isoforms. Cancer Res 53: 1226-1229.
76. Chefson A, Zhao J, Auclair K (2006) Replacement of natural cofactors by selected hydrogen peroxide donors or organic peroxides results in improved activity for CYP3A4 and CYP2D6. ChemBioChem 7: 916-919.
77. Bui PH, Hsu EL, Hankinson O (2009) Fatty acid hydroperoxides support cytochrome P450 2S1-mediated bioactivation of benzo[a]pyrene-7, 8-dihydrodiol. Mol Pharmacol 76: 1044-1052.
78. Sheng X, Zhang H, Im SC, Horner JH, Waskell L, Hollenberg PF, Newcomb M (2009) Kinetics of oxidation of benzphetamine by compounds I of cytochrome P450 2B4 and its mutants. J Am Chem Soc 131: 2971-2976.
79. Ortiz de Montellano PR, Choe YS, DePillis G, Catalano CE (1987) Structure-mechanism relationships in hemoproteins: oxygenations catalyzed by chloroperoxidase and horseradish peroxidase. J Biol Chem 262: 11641-11646.
80. Kania-Korwel I, Hrycay EG, Bandiera SM, Lehmler HJ (2008) 2, 20, 3, 30, 6, 60-Hexachlorobiphenyl (PCB 136) atropisomers interact enantioselectively with hepatic microsomal cytochrome P450 enzymes. Chem Res Toxicol 21: 1295-1303.
81. Lewis DFV (2002) Oxidative stress: the role of cytochromes P450 in oxygen activation. J Chem Technol Biotechnol 77: 1095-1100.
82. Doolittle RF, Feng DF, Tsang S, Cho G, Little E (1996) Determining divergence times of the major kingdoms of living organisms with a protein clock. Science 271: 470-477.
83. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527-605.
84. Payne AH, Hales DB (2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25: 947-970.
85. Kelly SL, Kelly DE, Jackson CJ, Warrilow AGS, Lamb DC (2005) The diversity and importance of microbial cytochromes P450. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 585-617.
86. Lamb DC, Lei L, Warrilow AGS, Lepesheva GI, Mullins JGL, Waterman MR, Kelly SL (2009) The first virally encoded cytochrome P450. J Virol 83: 8266-8269.
87. Kumar S (2010) Engineering cytochrome P450 biocatalysts for biotechnology, medicine and bioremediation. Expert Opin Drug Metab Toxicol 6: 115-131.
88. Renaud HJ, Cui JY, Khan M, Klaassen CD (2011) Tissue distribution and gender-divergent expression of 78 cytochrome P450 mRNAs in mice. Toxicol Sci 124: 261-277.
89. Norlin M, Wikvall K (2007) Enzymes in the conversion of cholesterol into bile acids. Curr Mol Med 7: 199-218.
90. Hasemann CA, Kurumbail RG, Boddupalli SS, Peterson JA, Deisenhofer J (1995) Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Structure 2: 41-62.
91. Gunsalus IC, Pederson TC, Sligar SG (1975) Oxygenase-catalyzed biological hydroxylations. Annu Rev Biochem 44: 377-407.
92. Poulos TL, Finzel BC, Howard AJ (1987) High-resolution crystal structure of cytochrome P450cam. J Mol Biol 195: 687-700.
93. Poulos TL, Raag R (1992) Cytochrome P450cam: crystallography, oxygen activation, and electron transfer. FASEB J 6: 674-679.
94. Sono M, Roach MP, Coulter ED, Dawson JH (1996) Heme-containing oxygenases. Chem Rev 96: 2841-2887.
95. Peterson JA, Graham SE (1998) A close family resemblance: the importance of structure in understanding cytochromes P450. Structure 6: 1079-1085.
96. Larsen AT, May EM, Auclair K (2011) Predictable stereoselective and chemoselective hydroxylations and epoxidations with P450 3A4. J Am Chem Soc 133: 7853-7858.
97. Scott EE, He YA, Wester MR, White MA, Chin CC, Halpert JR, Johnson EF, Stout CD (2003) An open conformation of mammalian cytochrome P450 2B4 at 1. 6-Åresolution. Proc Natl Acad Sci U S A 100: 13196-13201.
98. Poulos TL, Johnson EF (2005) Structures of cytochrome P450 enzymes. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 87-114.
99. Makris TM, Denisov I, Schlichting I, Sligar SG (2005) Activation of molecular oxygen by cytochrome P450. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 149-182.
100. Denisov IG, Makris TM, Sligar SG, Schlichting I (2005) Structure and chemistry of cytochrome P450. Chem Rev 105: 2253-2277.
101. Vatsis KP, Peng HM, Coon MJ (2005) Abolition of oxygenase function, retention of NADPH oxidase activity, and emergence of peroxidase activity upon replacement of the axial cysteine-436 ligand by histidine in cytochrome P450 2B4. Arch Biochem Biophys 434: 128-138.
102. Hernandez CE, Kumar S, Liu H, Halpert JR (2006) Investigation of the role of cytochrome P450 2B4 active site residues in substrate metabolism based on crystal structures of the ligand-bound enzyme. Arch Biochem Biophys 455: 61-67.
103. Baj-Rossi C, De Micheli G, Carrara S (2011) P450-based nano-bio-sensors for personalized medicine. In: Serra PA (ed) Biosensors-emerging materials and applications, InTech, Rijeka, Croatia, pp 447-482, ISBN: 978-953-307-328-6.
104. Omura T, Sato R (1964) The carbon monoxidebinding pigment of liver microsomes: I. Evidence for its hemoprotein nature. J Biol Chem 239: 2370-2378.
105. Estabrook RW (2003) A passion for P450s (remembrances of the early history of research on cytochrome P450). Drug Metab Dispos 31: 1461-1473.
106. Mason HS, North JC, Vanneste M (1965) Microsomal mixed-function oxidations: the metabolism of xenobiotics. Fed Proc 24: 1172-1180.
107. Dawson JH, Holm RH, Trudell JR, Barth G, Linder RE, Bunnenberg E, Djerassi C, Tang SC (1976) Oxidized cytochrome P-450: magnetic circular dichroism evidence for thiolate ligation in the substrate-bound form. Implications for the catalytic mechanism. J Am Chem Soc 98: 3707-3709.
108. Dawson JH, Sono M (1987) Cytochrome P-450 and chloroperoxidase: thiolate-ligated heme enzymes. Spectroscopic determination of their active site structures and mechanistic implications of thiolate ligation. Chem Rev 87: 1255-1276.
109. Auclair K, Moënne-Loccoz P, Ortiz de Montellano PR (2001) Roles of the proximal heme thiolate ligand in cytochrome P450cam. J Am Chem Soc 123: 4877-4885.
110. Nelson DR (2009) The cytochrome P450 homepage. Hum Genomics 4: 59-65.
111. Mueller EJ, Loida PJ, Sligar SG (1995) Twenty-five years of P450cam research: mechanistic insights into oxygenase catalysis. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 2nd edn. Plenum Press, New York, pp 83-124.
112. Testa B (1995) Reactions catalyzed by peroxidases. In: Testa B (ed) The metabolism of drugs and other xenobiotics: biochemistry of redox reactions. Academic Press, London, pp 346-388.
113. Porro CS (2011) Quantum mechanical/molecular mechanics studies of cytochrome P450BM3, PhD thesis, The University of Manchester, Manchester.
114. Gotoh O (1992) Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analysis of amino acid and coding nucleotide sequences. J Biol Chem 267: 83-90.
115. Poulos TL, Finzel BC, Howard AJ (1986) Crystal structure of substrate-free Pseudomonas putida cytochrome P450. Biochemistry 25: 5314-5322.
116. Ortiz de Montellano PR (1986) Oxygen activation and transfer. In: Ortiz de Montellano PR (ed) Cytochrome P-450: structure, mechanism, and biochemistry, 1st edn. Plenum Press, New York, pp 217-271.
117. Ortiz de Montellano PR (1995) Oxygen activation and reactivity. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 2nd edn. Plenum Press, New York, pp 245-304.
118. Meunier B, Bernadou J (2000) Active iron-oxo and iron-peroxo species in cytochromes P450 and peroxidases: oxo-hydroxo tautomerism with watersoluble metalloporphyrins. Struct Bond 97: 1-35.
119. Isaac IS, Dawson JH (1999) Haem iron-containing peroxidases. Essays Biochem 34: 51-69.
120. Jin S, Makris TM, Bryson TA, Sligar SG, Dawson JH (2003) Epoxidation of olefins by hydroperoxo-ferric cytochrome P450. J Am Chem Soc 125: 3406-3407.
121. Groves JT (2005) Models and mechanisms of cytochrome P450 action. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/Plenum Publishers, New York, pp 1-43.
122. Katagari M, Ganguli BN, Gunsalus IC (1968) A soluble cytochrome P-450 functional in methylene hydroxylation. J Biol Chem 243: 3543-3546.
123. Estabrook RW, Martinez-Zedillo G, Young S, Peterson JA, McCarthy J (1975) The interaction of steroids with liver microsomal cytochrome P-450-a general hypothesis. J Steroid Biochem 6: 419-425.
124. Guengerich FP, Johnson WW (1997) Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems. Biochemistry 36: 14741-14750.
125. Shaik S, Cohen S, Wang Y, Chen H, Kumar D, Thiel W (2010) P450 enzymes: their structure, reactivity, and selectivity-modeled by QM/MM calculations. Chem Rev 110: 949-1017.
126. Jung C (2011) The mystery of cytochrome P450 compound I: a mini-review dedicated to Klaus Ruckpaul. Biochim Biophys Acta 1814: 46-57.
127. Groves JT, McClusky GA (1976) Aliphatic hydroxylation via oxygen rebound. Oxygen transfer catalyzed by iron. J Am Chem Soc 98: 859-861.
128. Groves JT, McClusky GA, White RE, Coon MJ (1978) Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate. Biochem Biophys Res Commun 81: 154-160.
129. Jung C, de Vries S, Schünemann V (2011) Spectroscopic characterization of cytochrome P450 compound I. Arch Biochem Biophys 507: 44-55.
130. Hamilton GA (1969) Mechanisms of two-and four-electron oxidations catalyzed by some metalloenzymes. Adv Enzymol Relat Areas Mol Biol 32: 55-96.
131. O'Brien PJ (1978) Hydroperoxides and superoxides in microsomal oxidations. Pharmacol Ther 2: 517-536.
132. Higuchi T, Urano Y, Hirobe M, Nagano T (1998) Pronounced effects of axial thiolate ligation on oxygen activation by iron porphyrin. In: Ishimura Y, Shimada H, Suematsu M (eds) Oxygen homeostasis and its dynamics: Keio University symposia for life science and medicine, vol 1. Springer, Tokyo, pp 181-188.
133. Champion PM (1989) Elementary electronic excitations and the mechanism of cytochrome P450. J Am Chem Soc 111: 3434-3436.
134. Urano Y, Higuchi T, Hirobe M, Nagano T (1997) Pronounced axial thiolate ligand effect on the reactivity of high-valent oxo-iron porphyrin intermediate. J Am Chem Soc 119: 12008-12009.
135. Ohno T, Suzuki N, Dokoh T, Urano Y, Kikuchi K, Hirobe M, Higuchi T, Nagano T (2000) Remarkable axial thiolate ligand effect on the oxidation of hydrocarbons by active intermediate of iron porphyrin and cytochrome P450. J Inorg Biochem 82: 123-125.
136. Harischandra DN, Zhang R, Newcomb M (2005) Photochemical generation of a highly reactive iron-oxo intermediate: a true iron(V)-oxo species? J Am Chem Soc 127: 13776-13777.
137. Raner GM, Thompson JI, Haddy A, Tangham V, Bynum N, Reddy GR, Ballou DP, Dawson JH (2006) Spectroscopic investigations of intermediates in the reaction of cytochrome P450BM3-F87G with surrogate oxygen atom donors. J Inorg Biochem 100: 2045-2053.
138. Loida PJ, Sligar SG (1993) Molecular recognition in cytochrome P-450: mechanism for the control of uncoupling reactions. Biochemistry 32: 11530-11538.
139. McCarthy MB, White RE (1983) Functional differences between peroxidase compound I and the cytochrome P-450 reactive oxygen intermediate. J Biol Chem 258: 9153-9158.
140. Egawa T, Shimada H, Ishimura Y (1994) Evidence for compound I formation in the reaction of cytochrome P450cam with m-chloroperbenzoic acid. Biochem Biophys Res Commun 201: 1464-1469.
141. Auclair K, Hu Z, Little DM, Ortiz de Montellano PR, Groves JT (2002) Revisiting the mechanism of P450 enzymes with the radical clocks norcarane and spiro [2, 5]octane. J Am Chem Soc 124: 6020-6027.
142. Ortiz de Montellano PR, De Voss JJ (2002) Oxidizing species in the mechanism of cytochrome P450. Nat Prod Rep 19: 477-493.
143. Ortiz de Montellano PR (2010) Hydrocarbon hydroxylation by cytochrome P450 enzymes. Chem Rev 110: 932-948.
144. Hlavica P (2004) Models and mechanisms of O-O bond activation by cytochrome P450: a critical assessment of the potential role of multiple active intermediates in oxidative catalysis. Eur J Biochem 271: 4335-4360.
145. Schuler MA, Sligar SG (2007) Diversities and similarities in P450 systems: an introduction. Met Ions Life Sci 3: 1-26.
146. Lewis DFV, Pratt JM (1998) The P450 catalytic cycle and oxygenation mechanism. Drug Metab Rev 30: 739-786.
147. Rendic S (2002) Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 34: 83-448.
148. Hrycay E, Forrest D, Liu L, Wang R, Tai J, Deo A, Ling V, Bandiera S (2014) Hepatic bile acid metabolism and expression of cytochrome P450 and related enzymes are altered in Bsep-/-mice. Mol Cell Biochem 389: 119-132.
149. Hanukoglu I (1992) Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis. J Steroid Biochem Mol Biol 43: 779-804.
150. Groves JT, Han YZ (1995) Models and mechanisms of cytochrome P450 action. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 2nd edn. Plenum Press, New York, pp 3-48.
151. Guengerich FP, Munro AW (2013) Unusual cytochrome P450 enzymes and reactions. J Biol Chem 288: 17065-17073.
152. Erratico CA, Szeitz A, Bandiera SM (2012) Oxidative metabolism of BDE-99 by human liver microsomes: predominant role of CYP2B6. Toxicol Sci 129: 280-292.
153. Erratico C, Szeitz A, Bandiera SM (2013) Biotransformation of 2, 20, 4, 40-tetrabromodiphenyl ether (BDE-47) by human liver microsomes: identification of cytochrome P450 2B6 as the major enzyme involved. Chem Res Toxicol 26: 721-731.
154. Schnellmann RG, Putman CW, Sipes IG (1983) Metabolism of 2, 20, 3, 30, 6, 60-hexachlorobiphenyl and 2, 20, 4, 40, 5, 50-hexachlorobiphenyl by human hepatic microsomes. Biochem Pharmacol 32: 3233-3239.
155. Bandiera SM (2001) Cytochrome P450 enzymes as biomarkers of PCB exposure and modulators of toxicity. In: Robertson LW, Hansen LG (eds) PCBs: recent advances in environmental toxicology and health effects. University Press of Kentucky, Lexington, pp 185-192.
156. Wu X, Pramanik A, Duffel MW, Hrycay EG, Bandiera SM, Lehmler HJ, Kania-Korwel I (2011) 2, 20, 3, 30, 6, 60-hexachlorobiphenyl (PCB 136) is enantioselectively oxidized to hydroxylated metabolites by rat liver microsomes. Chem Res Toxicol 24: 2249-2257.
157. Lehmler HJ, Harrad SJ, Hühnerfuss H, Kania-Korwel I, Lee CM, Lu Z, Wong CS (2010) Chiral polychlorinated biphenyl transport, metabolism, and distribution: a review. Environ Sci Technol 44: 2757-2766.
158. Ishida C, Koga N, Hanioka N, Saeki HK, Yoshimura H (1991) Metabolism in vitro of 3, 4, 30, 40-and 2, 5, 20, 50-tetrachlorobiphenyl by rat liver microsomes and highly purified cytochrome P-450. J Pharmacobio Dyn 14: 276-284.
159. Waller SC, He YA, Harlow GR, He YQ, Mash EA, Halpert JR (1999) 2, 20, 3, 30, 6, 60-Hexachlorobiphenyl hydroxylation by active site mutants of cytochrome P450 2B1 and 2B11. Chem Res Toxicol 12: 690-699.
160. Deo AK, Bandiera SM (2008) Identification of human hepatic cytochrome P450 enzymes involved in the biotransformation of cholic and chenodeoxycholic acid. Drug Metab Dispos 36: 1983-1991.
161. Deo AK, Bandiera SM (2009) 3-Ketocholanoic acid is the major in vitro human hepatic microsomal metabolite of lithocholic acid. Drug Metab Dispos 37: 1938-1947.
162. Capdevila JH, Holla VR, Falck JR (2005) Cytochrome P450 and the metabolism and bioactivation of arachidonic acid and eicosanoids. In: Ortiz de Montellano PR (ed) Cytochrome P450: structure, mechanism, and biochemistry, 3rd edn. Kluwer Academic/PlenumPublishers, New York, pp 531-551.
163. Konkel A, Schunck WH (2011) Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim Biophys Acta 1814: 210-222.
164. Sharma PK, de Visser SP, Shaik S (2003) Can a single oxidant with two spin states masquerade as two different oxidants? A study of the sulfoxidation mechanism by cytochrome P450. J Am Chem Soc 125: 8698-8699.
165. Hecker M, Ullrich V (1989) On the mechanism of prostacyclin and thromboxane A2 biosynthesis. J Biol Chem 264: 141-150.
166. Gillam EMJ, Notley LM, Cai H, De Voss JJ, Guengerich FP (2000) Oxidation of indole by cytochrome P450 enzymes. Biochemistry 39: 13817-13824.
167. Ma X, Idle JR, Krausz KW, Gonzalez FJ (2005) Metabolism of melatonin by human cytochromes P450. Drug Metab Dispos 33: 489-494.
168. Bui P, Imaizumi S, Beedanagari SR, Reddy ST, Hankinson O (2011) Human CYP2S1 metabolizes cyclooxygenase-and lipoxygenase-derived eicosanoids. Drug Metab Dispos 39: 180-190.
169. George P (1953) The chemical nature of the second hydrogen peroxide compound formed by cytochrome c peroxidase and horseradish peroxidase. 1. Titration with reducing agents. Biochem J 54: 267-276.
170. Hollenberg PF (1992) Mechanisms of cytochrome P450 and peroxidase-catalyzed xenobiotic metabolism. FASEB J 6: 686-694.
171. Ator MA, Ortiz de Montellano PR (1987) Protein control of prosthetic heme reactivity: reaction of substrates with the heme edge of horseradish peroxidase. J Biol Chem 262: 1542-1551.
172. Newmyer SL, Sun J, Loehr TM, Ortiz de Montellano PR (1996) Rescue of the horseradish peroxidase His-170!Ala mutant activity by imidazole: importance of proximal ligand tethering. Biochemistry 35: 12788-12795.
173. Rahimtula AD, O'Brien PJ, Hrycay EG, Peterson JA, Estabrook RW (1974) Possible higher valence states of cytochrome P-450 during oxidative reactions. Biochem Biophys Res Commun 60: 695-702.
174. Hollenberg PF, Rand-Meir T, Hager LP (1974) The reaction of chlorite with horseradish peroxidase and chloroperoxidase: enzymatic chlorination and spectral intermediates. J Biol Chem 249: 5816-5825.
175. Kedderis GL, Koop DR, Hollenberg PF (1980) Ndemethylation reactions catalyzed by chloroperoxidase. J Biol Chem 255: 10174-10182.
176. Palcic MM, Rutter R, Araiso T, Hager LP, Dunford HB (1980) Spectrum of chloroperoxidase compound I. Biochem Biophys Res Commun 94: 1123-1127.
177. Wagner GC, Palcic MM, Dunford HB (1983) Absorption spectra of cytochrome P450cam in the reaction with peroxy acids. FEBS Lett 156: 244-248.
178. Rutter R, Valentine M, Hendrich MP, Hager LP, Debrunner PG (1983) Chemical nature of the porphyrin π cation radical in horseradish peroxidase. Biochemistry 22: 4769-4774.
179. Sivaraja M, Goodin DB, Smith M, Hoffman BM (1989) Identification by ENDOR of Trp191 as the free-radical site in cytochrome c peroxidase compound ES. Science 245: 738-740.
180. Schünemann V, Jung C, Terner J, Trautwein AX, Weiss R (2002) Spectroscopic studies of peroxyacetic acid reaction intermediates of cytochrome P450cam and chloroperoxidase. J Inorg Biochem 91: 586-596.
181. Spolitak T, Dawson JH, Ballou DP (2005) Reaction of ferric cytochrome P450cam with peracids: kinetic characterization of intermediates on the reaction pathway. J Biol Chem 280: 20300-20309.
182. Jung C, Schünemann V, Lendzian F, Trautwein AX, Contzen J, Galander M, Böttger LH, Richter M, Barra AL (2005) Spectroscopic characterization of the iron-oxo intermediate in cytochrome P450. Biol Chem 386: 1043-1053.
183. Jung C, Schünemann V, Lendzian F (2005) Freezequenched iron-oxo intermediates in cytochromes P450. Biochem Biophys Res Commun 338: 355-364.
184. Stone KL, Behan RK, Green MT (2005) X-ray absorption spectroscopy of chloroperoxidase compound I: insight into the reactive intermediate of P450 chemistry. Proc Natl Acad Sci U S A 102: 16563-16565.
185. Ullrich R, Hofrichter M (2005) The haloperoxidase of the agaric fungus Agrocybe aegerita hydroxylates toluene and naphthalene. FEBS Lett 579: 6247-6250.
186. Hofrichter M, Ullrich R (2006) Heme-thiolate haloperoxidases: versatile biocatalysts with biotechnological and environmental significance. Appl Microbiol Biotechnol 71: 276-288.
187. Ullrich R, Hofrichter M (2007) Enzymatic hydroxylation of aromatic compounds. Cell Mol Life Sci 64: 271-293.
188. Kinne M, Poraj-Kobielska M, Aranda E, Ullrich R, Hammel KE, Scheibner K, Hofrichter M (2009) Regioselective preparation of 5-hydroxypropranolol and 40-hydroxydiclofenac with a fungal peroxygenase. Bioorg Med Chem Lett 19: 3085-3087.
189. Poraj-Kobielska M, Kinne M, Ullrich R, Scheibner K, Kayser G, Hammel KE, Hofrichter M (2011) Preparation of human drug metabolites using fungal peroxygenases. Biochem Pharmacol 82: 789-796.
190. Gutirrez A, Babot ED, Ullrich R, Hofrichter M, Martínez AT, del Río JC (2011) Regioselective oxygenation of fatty acids, fatty alcohols and other aliphatic compounds by a basidiomycete heme-thiolate peroxidase. Arch Biochem Biophys 514: 33-43.
191. Kluge M, Ullrich R, Scheibner K, Hofrichter M (2012) Stereoselective benzylic hydroxylation of alkylbenzenes and epoxidation of styrene derivatives catalyzed by the peroxygenase of Agrocybe aegerita. Green Chem 14: 440-446.
192. Denisov IG, Dawson JH, Hager LP, Sligar SG (2007) The ferric-hydroperoxo complex of chloroperoxidase. Biochem Biophys Res Commun 363: 954-958.
193. Meharenna YT, Doukov T, Li H, Soltis SM, Poulos TL (2010) Crystallographic and single-crystal spectral analysis of the peroxidase ferryl intermediate. Biochemistry 49: 2984-2986.
194. Rittle J, Younker JM, Green MT (2010) Cytochrome P450: the active oxidant and its spectrum. Inorg Chem 49: 3610-3617.
195. Dolphin D, Forman A, Borg DC, Fajer J, Felton RH (1971) Compounds I of catalase and horseradish peroxidase: π-cation radicals. Proc Natl Acad Sci U S A 68: 614-618.
196. Yamada H, Yamazaki I (1974) Proton balance in conversions between five oxidation-reduction states of horseradish peroxidase. Arch Biochem Biophys 165: 728-738.
197. Loew GH, Harris DL (2000) Role of the heme active site and protein environment in structure, spectra, and function of the cytochrome P450s. Chem Rev 100: 407-419.
198. Morris DR, Hager LP (1966) Chloroperoxidase. I. Isolation and properties of the crystalline glycoprotein. J Biol Chem 241: 1763-1768.
199. Rai GP, Sakai S, Florez AM, Mogollon L, Hager LP (2001) Directed evolution of chloroperoxidase for improved epoxidation and chlorination catalysis. Adv Synth Catal 343: 638-645.
200. Blake RC II, Coon MJ (1989) On the mechanism of action of cytochrome P-450: spectral intermediates in the reaction with iodosobenzene and its derivatives. J Biol Chem 264: 3694-3701.
201. Wang X, Peter S, Kinne M, Hofrichter M, Groves JT (2012) Detection and kinetic characterization of a highly reactive heme-thiolate peroxygenase compound I. J Am Chem Soc 134: 12897-12900.
202. Wannstedt C, Rotella D, Siuda JF (1990) Chloroperoxidase mediated halogenation of phenols. Bull Environ Contam Toxicol 44: 282-287.
203. Geigert J, Neidleman SJ, Dalietos DJ (1983) Novel haloperoxidase substrates. Alkanes and cyclopropanes. J Biol Chem 258: 2273-2277.
204. Niu J, Yu G (2004) Molecular structural characteristics governing biocatalytic chlorination of PAHs by chloroperoxidase from Caldariomyces fumago. Environ Res 15: 159-167.
205. Doerge DR, Corbett MD (1991) Peroxygenation mechanism for chloroperoxidase-catalyzed N-oxidation of arylamines. Chem Res Toxicol 4: 556-560.
206. Colonna S, Gaggero N, Manfredi A, Casella L, Gullotti M, Carrea G, Pasta P (1990) Enantioselective oxidations of sulfides catalyzed by chloroperoxidases. Biochemistry 29: 10465-10468.
207. Green MT, Dawson JH, Gray HB (2004) Oxoiron (IV) in chloroperoxidase compound I is basic: implications for P450 chemistry. Science 304: 1653-1656.
208. Bell SR, Groves JT (2009) A highly reactive P450 model compound I. J Am Chem Soc 131: 9640-9641.
209. Reed CJ, DeMatteis F (1989) Cumene hydroperoxidedependent oxidation of N N N 0 N0-tetramethyl-pphenylenediamine and 7-ethoxycoumarin by cytochrome P-450. Biochem J 261: 793-800.
210. O'Brien PJ, Rahimtula A (1975) Involvement of cytochrome P-450 in the intracellular formation of lipid peroxides. J Agr Food Chem 23: 154-158.
211. Lindstrom TD, Aust SD (1984) Studies on cytochrome P-450-dependent lipid hydroperoxide reduction. Arch Biochem Biophys 233: 80-87.
212. Weiss RH, Arnold JL, Estabrook RW (1987) Transformation of an arachidonic acid hydroperoxide into epoxyhydroxy and trihydroxy fatty acids by liver microsomal cytochrome P-450. Arch Biochem Biophys 252: 334-338.
213. Vaz ADN, Coon MJ (1987) Hydrocarbon formation in the reductive cleavage of hydroperoxides by cytochrome P-450. Proc Natl Acad Sci U S A 84: 1172-1176.
214. Vaz ADN, Roberts ES, Coon MJ (1990) Reductive β-scission of the hydroperoxides of fatty acids and xenobiotics: role of alcohol-inducible cytochrome P-450. Proc Natl Acad Sci U S A 87: 5499-5503.
215. Tan L, Hrycay EG, Matsumoto K (1983) Synthesis and properties of the epimeric 6-hydroperoxyandrostenediones, new substrates/inhibitors of human placental aromatase. J Steroid Biochem 19: 1329-1338.
216. Hecker M, Baader WJ, Weber P, Ullrich V (1987) Thromboxane synthase catalyses hydroxylations of prostaglandin H2 analogs in the presence of iodosylbenzene. Eur J Biochem 169: 563-569.
217. Plastaras JP, Guengerich FP, Nebert DW, Marnett LJ (2000) Xenobiotic-metabolizing cytochromes P450 convert prostaglandin endoperoxide to hydroxyheptadecatrienoic acid and the mutagen, malondialdehyde. J Biol Chem 275: 11784-11790.
218. Chang MS, Boeglin WE, Guengerich FP, Brash AR (1996) Cytochrome P450-dependent transformations of 15R-and 15S-hydroperoxyeicosatetraenoic acids: stereoselective formation of epoxy alcohol products. Biochemistry 35: 464-471.
219. Rahimtula AD, O'Brien PJ, Seifried HE, Jerina DM (1978) The mechanism of action of cytochrome P-450. Occurrence of the 'NIH shift' during hydroperoxide-dependent aromatic hydroxylation. Eur J Biochem 89: 133-141.
220. Cederbaum AI (1983) Organic hydroperoxidedependent oxidation of ethanol by microsomes: lack of a role for free hydroxyl radicals. Arch Biochem Biophys 227: 329-338.
221. Hutzler JM, Powers FJ, Wynalda MA, Wienkers LC (2003) Effect of carbonate anion on cytochrome P450 2D6-mediated metabolism in vitro: the potential role of multiple oxygenating species. Arch Biochem Biophys 417: 165-175.
222. Rahimtula AD, O'Brien PJ (1974) Hydroperoxide catalyzed liver microsomal aromatic hydroxylation reactions involving cytochrome P-450. Biochem Biophys Res Commun 60: 440-447.
223. Capdevila J, Estabrook RW, Prough RA (1980) Differences in the mechanism of NADPH-and cumene hydroperoxide-supported reactions of cytochrome P-450. Arch Biochem Biophys 200: 186-195.
224. Cavalieri EL, Rogan EG, Cremonesi P, Devanesan PD (1988) Radical cations as precursors in the metabolic formation of quinones from benzo[a]pyrene and 6-fluorobenzo[a]pyrene: fluoro substitution as a probe for one-electron oxidation in aromatic substrates. Biochem Pharmacol 37: 2173-2182.
225. Hlavica P, Golly I, Mietaschk J (1983) Comparative studies on the cumene hydroperoxide-and NADPHsupported N-oxidation of 4-chloroaniline by cytochrome P-450. Biochem J 212: 539-547.
226. Miwa GT, Levin W, Thomas PE, Lu AYH (1978) The direct oxidation of ethanol by a catalase-and alcohol dehydrogenase-free reconstituted system containing cytochrome P-450. Arch Biochem Biophys 187: 464-475.
227. Rahimtula AD, O'Brien PJ (1975) Hydroperoxide dependent O-dealkylation reactions catalyzed by liver microsomal cytochrome P450. Biochem Biophys Res Commun 62: 268-275.
228. Ellin Å, Orrenius S (1975) Hydroperoxide-supported cytochrome P-450-linked fatty acid hydroxylation in liver microsomes. FEBS Lett 50: 378-381.
229. Danielsson H, Wikvall K (1976) On the ability of cumene hydroperoxide and NaIO4 to support microsomal hydroxylations in biosynthesis and metabolism of bile acids. FEBS Lett 66: 299-302.
230. Blake RC II, Coon MJ (1981) On the mechanism of action of cytochrome P-450: evaluation of homolytic and heterolytic mechanisms of oxygen-oxygen bond cleavage during substrate hydroxylation by peroxides. J Biol Chem 256: 12127-12133.
231. Yun CH, Miller GP, Guengerich FP (2000) Ratedetermining steps in phenacetin oxidations by human cytochrome P450 1A2 and selected mutants. Biochemistry 39: 11319-11329.
232. Otton SV, Gillam EM, Lennard MS, Tucker GT, Woods HF (1990) Propranolol oxidation by human liver microsomes-the use of cumene hydroperoxide to probe isoenzyme specificity and regio-and stereoselectivity. Br J Clin Pharmacol 30: 751-760.
233. Bui Q, Weisz J (1988) Identification of microsomal, organic hydroperoxide-dependent catechol estrogen formation: comparison with NADPH-dependent mechanism. Pharmacology 36: 356-364.
234. Spink DC, Spink BC, Zhuo X, Hussain MM, Gierthy JF, Ding X (2000) NADPH-and hydroperoxidesupported 17β-estradiol hydroxylation catalyzed by a variant form (432L, 453S) of human cytochrome P450 1B1. J Steroid Biochem Mol Biol 74: 11-18.
235. Edwards PR, Hrycay EG, Bandiera SM (2007) Differential inhibition of hepatic microsomal alkoxyresorufin O-dealkylation activities by tetrachlorobiphenyls. Chem Biol Interact 169: 42-52.
236. Nagata C, Tagashira Y, Kodama M (1974) Metabolic activation of BaP: significance of the free radical. In: Ts'o POP, DiPaolo JA (eds) Chemical carcinogenesis, part A. Marcel Dekker, New York, pp 87-111.
237. Lesko S, Caspary W, Lorentzen R, Ts'o POP (1975) Enzymic formation of 6-oxobenzo[a]pyrene radical in rat liver homogenates from carcinogenic benzo[a] pyrene. Biochemistry 14: 3978-3984.
238. McCarthy MB, White RE (1983) Competing modes of peroxyacid flux through cytochrome P-450. J Biol Chem 258: 11610-11616.
239. Lee WA, Bruice TC (1985) Homolytic and heterolytic oxygen-oxygen bond scissions accompanying oxygen transfer to iron (III) porphyrins by percarboxylic acids and hydroperoxides: a mechanistic criterion for peroxidase and cytochrome P-450. J Am Chem Soc 107: 513-514.
240. Green MT (2009) C-H bond activation in heme proteins: the role of thiolate ligation in cytochrome P450. Curr Opin Chem Biol 13: 84-88.
241. Krest CM, Onderko EL, Yosca TH, Calixto JC, Karp RF, Livada J, Rittle J, Green MT (2013) Reactive intermediates in cytochrome P450 catalysis. J Biol Chem 288: 17074-17081.
242. Davydov R, Macdonald IDG, Makris TM, Sligar SG, Hoffman BM (1999) EPR and ENDOR of catalytic intermediates in cryoreduced native and mutant oxy-cytochromes P450cam: mutation-induced changes in the proton delivery system. J Am Chem Soc 121: 10654-10655.
243. Heimbrook DC, Murray RI, Egeberg KD, Sligar SG, Nee MW, Bruice TC (1984) Demethylation of N, N-dimethylaniline and p-cyano-N, N-dimethylaniline and their N-oxides by cytochromes P450LM2 and P450CAM. J Am Chem Soc 106: 1514-1515.
244. Shaffer CL, Harriman S, Koen YM, Hanzlik RP (2002) Formation of cyclopropanone during cytochrome P450-catalyzed N-dealkylation of a cyclopropylamine. J Am Chem Soc 124: 8268-8274.
245. Dowers TS, Rock DA, Rock DA, Jones JP (2004) Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450-catalyzed N-dealkylation. J Am Chem Soc 126: 8868-8869.
246. Roberts KM, Jones JP (2010) Anilinic N-oxides support cytochrome P450-mediated N-dealkylation through hydrogen-atom transfer. Chem Eur J 16: 8096-8107.
247. Golly I, Hlavica P, Wolf J (1984) The role of lipid peroxidation in the N-oxidation of 4-chloroaniline. Biochem J 224: 415-421.
248. Spolitak T, Dawson JH, Ballou DP (2008) Replacement of tyrosine residues by phenylalanine in cytochrome P450cam alters the formation of Cpd II-like species in reactions with artificial oxidants. J Biol Inorg Chem 13: 599-611.
249. Green MT (1999) Evidence for sulfur-based radicals in thiolate compound I intermediates. J Am Chem Soc 121: 7939-7940.
250. Loew GH, Collins J, Luke B, Waleh A, Padzianowski A (1986) Theoretical studies of cytochrome P-450: characterization of stable and transient active states, reaction mechanisms and substrate-enzyme interactions. Enzyme 36: 54-78.
251. Shaik S, Filatov M, Schröder D, Schwarz H (1998) Electronic structure makes a difference: cytochrome P-450 mediated hydroxylations of hydrocarbons as a two-state reactivity paradigm. Chem Eur J 4: 193-199.
252. Urano Y, Higuchi T, Hirobe M (1996) Substratedependent changes of the oxidative O-dealkylation mechanism of several chemical and biological oxidizing systems. J Chem Soc Perkin Trans 2: 1169-1173.
253. Lindsay-Smith JR, Sleath PR (1983) Model systems for cytochrome P450 dependent mono-oxygenases. Part 2. Kinetic isotope effects for the oxidative demethylation of anisole and [Me-H3]anisole by cytochrome P450 dependent mono-oxygenases and model systems. J Chem Soc Perkin Trans 2: 621-628.
254. Pan Z, Wang RQ, Sheng X, Horner JH, Newcomb M (2009) Highly reactive porphyrin-iron-oxo derivatives produced by photolysis of metastable porphyrin-iron(IV) diperchlorates. J Am Chem Soc 131: 2621-2628.
255. Isobe H, Yamaguchi K, Okumura M, Shimada J (2012) Role of perferryl-oxo oxidant in alkane hydroxylation catalyzed by cytochrome P450: a hybrid density functional study. J Phys Chem B 116: 4713-4730.
256. Altun A, Shaik S, Thiel W (2007) What is the active species of cytochrome P450 during camphor hydroxylation? QM/MM studies of different electronic states of compound I and of reduced and oxidized iron-oxo intermediates. J Am Chem Soc 129: 8978-8987.
257. Nam W, Park SE, Lim IK, Lim MH, Hong J, Kim J (2003) First direct evidence for stereospecific olefin epoxidation and alkane hydroxylation by an oxoiron (IV) porphyrin complex. J Am Chem Soc 125: 14674-14675.
258. Shaik S, Kumar D, de Visser SP, Altun A, Thiel W (2005) Theoretical perspective on the structure and mechanism of cytochrome P450 enzymes. Chem Rev 105: 2279-2328.
259. Ogliaro F, de Visser SP, Cohen S, Sharma PK, Shaik S (2002) Searching for the second oxidant in the catalytic cycle of cytochrome P450: a theoretical investigation of the iron(III)-hydroperoxo species and its epoxidation pathways. J Am Chem Soc 124: 2806-2817.
260. Yosca TH, Rittle J, Krest CM, Onderko EL, Silakov A, Calixto JC, Behan RK, Green MT (2013) Iron(IV)hydroxide pKa and the role of thiolate ligation in C-H bond activation by cytochrome P450. Science 342: 825-829.
261. Schünemann V, Lendzian F, Jung C, Contzen J, Barra AL, Sligar SG, Trautwein AX (2004) Tyrosine radical formation in the reaction of wild type and mutant cytochrome P450cam with peroxy acids: a multifrequency EPR study of intermediates on the millisecond time scale. J Biol Chem 279: 10919-10930.
262. Spolitak T, Dawson JH, Ballou DP (2006) Rapid kinetics investigations of peracid oxidation of ferric cytochrome P450cam: nature and possible function of compound ES. J Inorg Biochem 100: 2034-2044.
263. Sivaramakrishnan S, Ouellet H, Matsumura H, Guan S, Moënne-Loccoz P, Burlingame AL, Ortiz de Montellano PR (2012) Proximal ligand electron donation and reactivity of the cytochrome P450 ferric-peroxo anion. J Am Chem Soc 134: 6673-6684.
264. Davydov R, Makris TM, Kofman V, Werst DE, Sligar SC, Hoffman BM (2001) Hydroxylation of camphor by reduced oxy-cytochrome P450cam: mechanistic implications of EPR and ENDOR studies of catalytic intermediates in native and mutant enzymes. J Am Chem Soc 123: 1403-1415.
265. Davydov R, Hoffman BM (2011) Active intermediates in heme monooxygenase reactions as revealed by cryoreduction/annealing, EPR/ENDOR studies. Arch Biochem Biophys 507: 36-43.
266. Luthra A, Denisov IG, Sligar SG (2011) Spectroscopic features of cytochrome P450 reaction intermediates. Arch Biochem Biophys 507: 26-35.
267. Davydov R, Dawson JH, Perera R, Hoffman BM (2013) The use of deuterated camphor as a substrate in 1H ENDOR studies of hydroxylation by cryoreduced oxy P450cam provides new evidence of the involvement of compound I. Biochemistry 52: 667-671.
268. Yoshioka S, Takahashi S, Ishimori K, Morishima I (2000) Roles of the axial push effect in cytochrome P450cam studied with the site-directed mutagenesis at the heme proximal site. J Inorg Biochem 81: 141-151.
269. Rutter R, Hager LP, Dhonau H, Hendrich MP, Hager LP, Debrunner PG (1984) Chloroperoxidase compound I: electron paramagnetic resonance and Mössbauer studies. Biochemistry 22: 6808-6816.
270. Meunier B, de Visser SP, Shaik S (2004) Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chem Rev 104: 3947-3980.
271. Schlichting I, Berendzen J, Chu K, Stock AM, Maves SA, Benson DE, Sweet RM, Ringe D, Petsko GA, Sligar SG (2000) The catalytic pathway of cytochrome P450cam at atomic resolution. Science 287: 1615-1622.
272. Imai M, Shimada H, Watanabe Y, Matsushima-Hibiya Y, Makino R, Koga H, Horiuchi T, Ishimura Y (1989) Uncoupling of the cytochrome P-450cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: a possible role of the hydroxy amino acid in oxygen activation. Proc Natl Acad Sci U S A 86: 7823-7827.
273. Martinis SA, Atkins WM, Stayton PS, Sligar SG (1989) A conserved residue of cytochrome P-450 is involved in heme-oxygen stability and activation. J Am Chem Soc 111: 9252-9253.
274. Vidakovic M, Sligar SG, Li H, Poulos TL (1998) Understanding the role of the essential Asp251 in cytochrome P450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Biochemistry 37: 9211-9219.
275. Raag R, Martinis SA, Sligar SG, Poulos TL (1991) Crystal structure of the cytochrome P-450cam active site mutant Thr252Ala. Biochemistry 30: 11420-11429.
276. Gerber NC, Sligar SG (1992) Catalytic mechanism of cytochrome P-450: evidence for a distal charge relay. J Am Chem Soc 114: 8742-8743.
277. Gerber NC, Sligar SG (1994) A role for Asp-251 in cytochrome P-450cam oxygen activation. J Biol Chem 269: 4260-4266.
278. Chandrasena REP, Vatsis KP, Coon MJ, Hollenberg PF, Newcomb M (2004) Hydroxylation by the hydroperoxy-iron species in cytochrome P450 enzymes. J Am Chem Soc 126: 115-126.
279. Sevrioukova IF, Poulos TL (2011) Structural biology of redox partner interactions in P450cam monooxygenase: a fresh look at an old system. Arch Biochem Biophys 507: 66-74.
280. Poulos TL, Madrona Y (2013) Oxygen activation and redox partner binding in cytochromes P450. Biotechnol Appl Biochem 60: 128-133.
281. Yonetani T, Schleyer H (1967) Studies on cytochrome c peroxidase: IX. The reaction of ferrimyoglobin with hydroperoxides and a comparison of peroxide-induced compounds of ferrimyoglobin and cytochrome c peroxidase. J Biol Chem 242: 1974-1979.
282. Sligar SG, Kennedy KA, Pearson DC (1982) The chemical basis of mixed function oxidation. In: King TE, Mason HS, Morrison M (eds) Oxidases and related redox systems. Permagon Press, Oxford, pp 837-856.
283. Gustafsson JÅ, Rondahl L, Bergman J (1979) Iodosylbenzene derivatives as oxygen donors in cytochrome P-450 catalyzed steroid hydroxylations. Biochemistry 18: 865-870.
284. Macdonald TL, Gutheim WG, Martin RB, Guengerich FP (1989) Oxidation of substituted N, N-dimethylanilines by cytochrome P-450: estimation of the effective oxidation-reduction potential of cytochrome P-450. Biochemistry 28: 2071-2077.
285. Lichtenberger F, Nastainczyk W, Ullrich V (1976) Cytochrome P450 as an oxene transferase. Biochem Biophys Res Commun 70: 939-946.
286. Gustafsson JÅ, Bergman J (1976) Iodine-and chlorine-containing oxidation agents as hydroxylating catalysts in cytochrome P-450-dependent fatty acid hydroxylation reactions in rat liver microsomes. FEBS Lett 70: 276-280.
287. Berg A, Ingelman-Sundberg M, Gustafsson JÅ (1979) Purification and characterization of cytochrome P-450meg. J Biol Chem 254: 5264-5271.
288. Yamazaki H, Ueng YF, Shimada T, Guengerich FP (1995) Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH-cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates. Biochemistry 34: 8380-8389.
289. Glieder A, Farinas ET, Arnold FH (2002) Laboratory evolution of a soluble, self-sufficient, highly active alkane hydroxylase. Nat Biotechnol 20: 1135-1139.
290. Shaik S, de Visser SP, Kumar D (2004) One oxidant, many pathways: a theoretical perspective of monooxygenation mechanisms by cytochrome P450 enzymes. J Biol Inorg Chem 9: 661-668.
291. Cho KB, Moreau Y, Kumar D, Rock DA, Jones JP, Shaik S (2007) Formation of the active species of cytochrome P450 by using iodosylbenzene: a case for spin-selective reactivity. Chem Eur J 13: 4103-4115.
292. Akhtar M, Corina DL, Pratt J, Smith T (1976) Studies on the removal of C-19 in oestrogen biosynthesis using 18O2. J Chem Soc Chem Commun 21: 854-856.
293. Akhtar M, Calder MR, Corina DL, Wright JN (1982) Mechanistic studies on C-19 demethylation in oestrogen biosynthesis. Biochem J 201: 569-580.
294. Akhtar M, Njar VCO, Wright JN (1993) Mechanistic studies on aromatase and related C-C bond cleaving P-450 enzymes. J Steroid Biochem Mol Biol 44: 375-387.
295. Akhtar M, Wright JN, Lee-Robichaud P (2011) A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17, 20-lyase (CYP17). J Steroid Biochem Mol Biol 125: 2-12.
296. Gantt SI, Denisov IG, Grinkova YV, Sligar SG (2009) The critical iron-oxygen intermediate in human aromatase. Biochem Biophys Res Commun 387: 169-173.
297. Hackett JC, Brueggemeier RW, Hadad CM (2005) The final catalytic step of cytochrome P450 aromatase: a density functional theory study. J Am Chem Soc 127: 5224-5237.
298. Vaz ADN, Roberts ES, Coon MJ (1991) Olefin formation in the oxidative deformylation of aldehydes by cytochrome P-450: mechanistic implications for catalysis by oxygen-derived peroxide. J Am Chem Soc 113: 5886-5887.
299. Roberts ES, Vaz ADN, Coon MJ (1991) Catalysis by cytochrome P-450 of an oxidative reaction in xenobiotic aldehyde metabolism: deformylation with olefin formation. Proc Natl Acad Sci U S A 88: 8963-8966.
300. Vaz ADN, Pernecky SJ, Raner GM, Coon MJ (1996) Peroxo-iron and oxenoid-iron species as alternative oxygenating agents in cytochrome P450-catalyzed reactions: switching by threonine-302 to alanine mutagenesis of cytochrome P450 2B4. Proc Natl Acad Sci U S A 93: 4644-4648.
301. Vaz ADN, McGinnity DF, Coon MJ (1998) Epoxidation of olefins by cytochrome P450: evidence from site-specific mutagenesis for hydroperoxo-iron as an electrophilic oxidant. Proc Natl Acad Sci U S A 95: 3555-3560.
302. Newcomb M, Le Tadic MH, Putt DA, Hollenberg PF (1995) An incredibly fast apparent oxygen rebound rate constant for hydrocarbon hydroxylation by cytochrome P-450 enzymes. J Am Chem Soc 117: 3312-3313.
303. Newcomb M, Le Tadic-Biadatti MH, Chestney DL, Roberts ES, Hollenberg PF (1995) A nonsynchronous concerted mechanism for cytochrome P-450 catalyzed hydroxylation. J Am Chem Soc 117: 12085-12091.
304. Toy PH, Newcomb M, Coon MJ, Vaz ADN (1998) Two distinct electrophilic oxidants effect hydroxylation in cytochrome P-450-catalyzed reactions. J Am Chem Soc 120: 9718-9719.
305. Newcomb M, Toy PH (2000) Hypersensitive radical probes and the mechanisms of cytochrome P450-catalyzed hydroxylation reactions. Acc Chem Res 33: 449-455.
306. Newcomb M, Shen R, Choi SY, Toy PH, Hollenberg PF, Vaz ADN, Coon MJ (2000) Cytochrome P450-catalyzed hydroxylation of mechanistic probes that distinguish between radicals and cations: evidence for cationic but not for radical intermediates. J Am Chem Soc 122: 2677-2686.
307. Newcomb M, Aebisher D, Shen R, Chandrasena REP, Hollenberg PF, Coon MJ (2003) Kinetic isotope effects implicate two electrophilic oxidants in cytochrome P450-catalyzed hydroxylations. J Am Chem Soc 125: 6064-6065.
308. Volz TJ, Rock DA, Jones JP (2002) Evidence for two different active oxygen species in cytochrome P450 BM3 mediated sulfoxidation and N-dealkylation reactions. J Am Chem Soc 124: 9724-9725.
309. Watanabe Y (2001) Alternatives to the oxoferryl porphyrin cation radical as the proposed reactive intermediate of cytochrome P450: two-electron oxidized Fe(III) porphyrin derivatives. J Biol Inorg Chem 6: 846-856.
310. Shaik S, Cohen S, de Visser SP, Sharma PK, Kumar D, Kozuch S, Ogliaro F, Danovich D (2004) The "rebound controversy": an overview and theoretical modeling of the rebound step in C-H hydroxylation by cytochrome P450. Eur J Inorg Chem 2004: 207-226.
311. de Visser SP, Ogliaro F, Sharma PK, Shaik S (2002) What factors affect the regioselectivity of oxidation by cytochrome P450? A DFT study of allylic hydroxylation and double bond epoxidation in a model reaction. J Am Chem Soc 124: 11809-11826.
312. Goto Y, Matsui T, Ozaki S, Watanabe Y, Fukuzumi S (1999) Mechanisms of sulfoxidation catalyzed by high-valent intermediates of heme enzymes: electron-transfer vs oxygen-transfer mechanism. J Am Chem Soc 121: 9497-9502.
313. Krauser JA, Guengerich FP (2005) Cytochrome P450 3A4-catalyzed testosterone 6β-hydroxylation stereochemistry, kinetic deuterium isotope effects, and rate-limiting steps. J Biol Chem 280: 19496-19506.
314. Tanaka K, Kurihara N, NakajimaM (1979) Oxidative metabolism of tetrachlorocyclohexenes, pentachlorocyclohexenes, and hexachlorocyclohexenes with microsomes from rat liver and house fly abdomen. Pestic Biochem Physiol 10: 79-95.
315. Groves JT, Subramanian DV (1984) Hydroxylation by cytochrome P-450 and metalloporphyrin models: evidence for allylic rearrangement. J Am Chem Soc 106: 2177-2181.
316. Oliw EH, Brodowsky ID, Hörnsten L, Hamberg M (1993) Bis-Allylic hydroxylation of polyunsaturated fatty acids by hepatic monooxygenases and its relation to the enzymatic and nonenzymatic formation of conjugated hydroxy fatty acids. Arch Biochem Biophys 300: 434-439.
317. Ortiz de Montellano PR, Stearns RA (1987) Timing of the radical recombination step in cytochrome P-450 catalysis with ring-strained probes. J Am Chem Soc 109: 3415-3420.
318. Bowry VW, Ingold KU (1991) A radical clock investigation of microsomal cytochrome P-450 hydroxylation of hydrocarbons: rate of oxygen rebound. J Am Chem Soc 113: 5699-5707.
319. Atkinson JK, Ingold KU (1993) Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes. Biochemistry 32: 9209-9214.
320. Kumar D, de Visser SP, Shaik S (2003) How does product isotope effect prove the operation of a two-state "rebound" mechanism in C-H hydroxylation by cytochrome P450? J Am Chem Soc 125: 13024-13025.
321. de Visser SP, Porro CS, Quesne MG, Sainna MA, Munro AW (2014) Overview on theoretical studies discriminating the two-oxidant versus two-statereactivity models for substrate monooxygenation by cytochrome P450 enzymes. Curr Topics Med Chem 13: 2218-2232.
322. Wang B, Li C, Cho K, Nam W, Shaik S (2013) The FeIII(H2O2) complex as a highly efficient oxidant in sulfoxidation reactions: revival of an underrated oxidant in cytochrome P450. J Chem Theory Comput 9: 2519-2525.
323. Gillam EMJ, Guengerich FP (2001) Exploiting the versatility of human cytochrome P450 enzymes: the promise of blue roses from biotechnology. IUBMB Life 52: 271-277.
324. Guengerich FP (2002) Cytochrome P450 enzymes in the generation of commercial products. Nat Rev Drug Discov 1: 359-366.
325. Kumar S, Halpert JR (2005) Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. Biochem Biophys Res Commun 338: 456-464.
326. Roy P, Waxman DJ (2006) Activation of oxazaphosphorines by cytochrome P450: application to genedirected enzyme prodrug therapy for cancer. Toxicol In Vitro 20: 176-186.
327. Purnapatre K, Khattar SK, Saini KS (2008) Cytochrome P450s in the development of target-based anticancer drugs. Cancer Lett 259: 1-15.
328. Hlavica P (2009) Assembly of non-natural electron transfer conduits in the cytochrome P450 system: a critical assessment and update of artificial redox constructs amenable to exploitation in biotechnological areas. Biotechnol Adv 27: 103-121.
329. Di Nardo G, Fantuzzi A, Sideri A, Panicco P, Sassone C, Giunta C, Gilardi G (2007) Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by human liver enzymes. J Biol Inorg Chem 12: 313-323.
330. Fasan R (2012) Tuning P450 enzymes as oxidation catalysts. ACS Catal 2: 647-666.
331. Meinhold P, Peters MW, Chen MMY, Takahashi K, Arnold FH (2005) Direct conversion of ethane to ethanol by engineered cytochrome P450 BM3. ChemBioChem 6: 1765-1768.
332. Fasan R, Chen MM, Crook NC, Arnold FH (2007) Engineered alkane-hydroxylating cytochrome P450BM3 exhibiting native-like catalytic properties. Angew Chem Int Ed 46: 8414-8418.
333. Fasan R, Meharenna YT, Snow CD, Poulos TL, Arnold FH (2008) Evolutionary history of a specialized P450 propane monooxygenase. J Mol Biol 383: 1069-1080.
334. Sawayama AM, Chen MMY, Kulanthaivel P, Kuo MS, Hemmerle H, Arnold FH (2009) A panel of cytochrome P450 BM3 variants to produce drug metabolites and diversify lead compounds. Chem Eur J 15: 11723-11729.
335. Jung ST, Lauchli R, Arnold FH (2011) Cytochrome P450: taming a wild type enzyme. Curr Opin Biotechnol 22: 1-9.
336. Harford-Cross CF, Carmichael AB, Allan FK, England PA, Rouch DA, Wong LL (2000) Protein engineering of cytochrome P450CAM (CYP101) for the oxidation of polycyclic aromatic hydrocarbons. Protein Eng 13: 121-128.
337. Otey CR, Landwehr M, Endelman JB, Hiraga K, Bloom JD, Arnold FH (2006) Structure-guided recombination creates an artificial family of cytochromes P450. PLoS Biol 4: 789-798.
338. Li Y, Drummond DA, Sawayama AM, Snow CD, Bloom JD, Arnold FH (2007) A diverse family of thermostable cytochrome P450s created by recombination of stabilizing fragments. Nat Biotechnol 25: 1051-1056.
339. Huang W, Johnston WA, Hayes MA, De Voss JJ, Gillam EMJ (2007) A shuffled CYP2C library with a high degree of structural integrity and functional diversity. Arch Biochem Biophys 467: 193-205.
340. Wu ZL, Podust LM, Guengerich FP (2005) Expansion of substrate specificity of cytochrome P450 2A6 by random and site-directed mutagenesis. J Biol Chem 280: 41090-41100.
341. England PA, Harford-Cross CF, Stevenson JA, Rouch DA, Wong LL (1998) The oxidation of naphthalene and pyrene by cytochrome P450cam. FEBS Lett 424: 271-274.
342. Nickerson DP, Harford-Cross CF, Fulcher SR, Wong LL (1997) The catalytic activity of cytochrome P450cam towards styrene oxidation is increased by site-specific mutagenesis. FEBS Lett 405: 153-156.
343. Bell SG, Stevenson JA, Boyd HD, Campbell S, Riddle AD, Orton EL, Wong LL (2002) Butane and propane oxidation by engineered cytochrome P450cam. Chem Commun 5: 490-491.
344. Xu F, Bell SG, Lednik J, Insley A, Rao Z, Wong LL (2005) The heme monooxygenase cytochrome P450cam can be engineered to oxidize ethane to ethanol. Angew Chem Int Ed 44: 4029-4032.
345. Sulistyaningdyah WT, Ogawa J, Li QS, Maeda C, Yano Y, Schmid RD, Shimizu S (2005) Hydroxylation activity of P450 BM-3 mutant F87V towards aromatic compounds and its application to the synthesis of hydroquinone derivatives from phenolic compounds. Appl Microbiol Biotechnol 67: 556-562.
346. Carmichael AB, Wong LL (2001) Protein engineering of Bacillus megaterium CYP102. The oxidation of polycyclic aromatic hydrocarbons. Eur J Biochem 268: 3117-3125.
347. Li QS, Ogawa J, Schmid RD, Shimizu S (2001) Engineering cytochrome P450 BM-3 for oxidation of polycyclic aromatic hydrocarbons. Appl Environ Microbiol 67: 5735-5739.
348. Li HM, Mei LE, Urlacher VB, Schmid RD (2008) Cytochrome P450 BM-3 evolved by random and saturation mutagenesis as an effective indolehydroxylating catalyst. Appl Biochem Biotechnol 144: 27-36.
349. Koo LS, Immoos CE, Cohen MS, Farmer PJ, Ortiz de Montellano PR (2000) Enhanced electron transfer and lauric acid hydroxylation by sitedirected mutagenesis of CYP119. J Am Chem Soc 124: 5684-5691.
350. Kim D, Guengerich FP (2004) Enhancement of 7-methoxyresorufin O-demethylation activity of human cytochrome P450 1A2 by molecular breeding. Arch Biochem Biophys 432: 102-108.
351. Nakamura K, Martin MV, Guengerich FP (2001) Random mutagenesis of human cytochrome P450 2A6 and screening with indole oxidation products. Arch Biochem Biophys 395: 25-31.
352. Kubo T, Peters MW, Meinhold P, Arnold FH (2006) Enantioselective epoxidation of terminal alkenes to (R)-and (S)-epoxides by engineered cytochromes P450 BM-3. Chem Eur J 12: 1216-1220.
353. Rentmeister A, Arnold FH, Fasan R (2009) Chemoenzymatic fluorination of unactivated organic compounds. Nat Chem Biol 5: 26-28.
354. Lewis JC, Mantovani SM, Fu Y, Snow CD, Komor RS, Wong CH, Arnold FH (2010) Combinatorial alanine substitution enables rapid optimization of cytochrome P450BM3 for selective hydroxylation of large substrates. ChemBioChem 11: 2502-2505.
355. Dietrich JA, Yoshikuni Y, Fisher KJ, Woolard FX, Ockey D, McPhee DJ, Renninger NS, Chang MC, Baker D, Keasling JD (2009) A novel semibiosynthetic route for artemisinin production using engineered substrate-promiscuous P450(BM3). ACS Chem Biol 4: 261-267.
356. Landwehr M, Hochrein L, Otey CR, Kasrayan A, Bäckvall JE, Arnold FH (2006) Enantioselective α-hydroxylation of 2-arylacetic acid derivatives and buspirone catalyzed by engineered cytochrome P450 BM-3. J Am Chem Soc 128: 6058-6059.
357. van Vugt-Lussenburg BMA, Stjernschantz E, Lastdrager J, Oostenbrink C, Vermeulen NPE, Commandeur JNM (2007) Identification of critical residues in novel drug metabolizing mutants of cytochrome P450 BM3 using random mutagenesis. J Med Chem 50: 455-461.
358. Damsten MC, van Vugt-Lussenburg BMA, Zeldenthuis T, de Vlieger JSB, Commandeur JNM, Vermeulen NPE (2008) Application of drug metabolising mutants of cytochrome P450 BM3 (CYP102A1) as biocatalysts for the generation of reactive metabolites. Chem Biol Interact 171: 96-107.
359. Kim DH, Kim KH, Kim D, Jung HC, Pan JG, Chi YT, Ahn T, Yun CH (2010) Oxidation of human cytochrome P450 1A2 substrates by Bacillus megaterium cytochrome P450 BM3. J Mol Catal B Enzym 63: 179-187.
360. Kim KH, Kang JY, Kim DH, Park SH, Park SH, Kim D, Park KD, Lee YJ, Jung HC, Pan JG, Ahn T, Yun CH (2011) Generation of human chiral metabolites of simvastatin and lovastatin by bacterial CYP102A1 mutants. Drug Metab Dispos 39: 140-150.
361. Bistolas N, Wollenberger U, Jung C, Scheller FW (2005) Cytochrome P450 biosensors a review. Biosens Bioelectron 20: 2408-2423.
362. Gillam EMJ, Aguinaldo AMA, Notley LM, Kim D, Mundkowski RG, Volkov AA, Arnold FH, Souček P, De Voss JJ, Guengerich FP (1999) Formation of indigo by recombinant mammalian cytochrome P450. Biochem Biophys Res Commun 265: 469-472.
363. Kim D, Guengerich FP (2004) Selection of human cytochrome P450 1A2 mutants with enhanced catalytic activity for heterocyclic amine N-hydroxylation. Biochemistry 43: 981-988.
364. Adachi J, Mori Y, Matsui S, Takigami H, Fujino J, Kitagawa H, Miller CA III, Kato T, Saeki K, Matsuda T (2001) Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. J Biol Chem 276: 31475-31478.
365. Kumar S, Scott EE, Liu H, Halpert JR (2003) A rational approach to re-engineer cytochrome P450 2B1 regioselectivity based on the crystal structure of cytochrome P450 2C5. J Biol Chem 278: 17178-17184.
366. Fujishiro T, Shoji O, Nagano S, Sugimoto H, Shiro Y, Watanabe Y (2011) Crystal structure of H2O2-dependent cytochrome P450SPα with its bound fatty acid substrate: insight into the regioselective hydroxylation of fatty acids at the α position. J Biol Chem 286: 29941-29950.
367. Keizers PHJ, Schraven LHM, de Graaf C, Hidestrand M, Ingelman-Sundberg M, van Dijk BR, Vermeulen NPE, Commandeur JNM (2005) Role of the conserved threonine 309 in mechanism of oxidation by cytochrome P450 2D6. Biochem Biophys Res Commun 338: 1065-1074.
368. Yooseph S, Sutton G, Rusch DB, Halpern AL, Williamson SK, Remington K, Eisen JA, Heidelberg KB, Manning G, Li W, Venter JC (2007) The sorcerer II global ocean sampling expedition: expanding the universe of protein families. PLoS Biol 5: 432-466. e16. doi: 10. 1371/journal. pbio. 0050016.
369. Rusch DB, Halpern AL, Sutton G, Heidelberg KB, Williamson S, Yooseph S, Wu D, Eisen JA, Hoffman JM, Remington K, Venter JC (2007) The sorcerer II global ocean sampling expedition: Northwest Atlantic through Eastern Tropical Pacific. PLoS Biol 5: 398-431. e77. doi: 10. 1371/journal. pbio. 0050077.
370. Kannan N, Taylor SS, Zhai Y, Venter JC, Manning G (2007) Structural and functional diversity of the microbial kinome. PLoS Biol 5(467-478): e17. doi: 10. 1371/journal. pbio. 0050017.
371. Nelson DR (2007) The evolution and genomics of cytochrome P450, drnelson. uthsc. edu/talks/UTSAshorttalk. pdf.
372. Müller WJ (2012) Cytochrome P450 monooxygenases from extremophiles, PhD thesis, University of the Free State, Bloemfontein, Republic of South Africa.