High-througput enzymology and combinatorial mutagenesis for mining cytochrome P450 functions

Expert Opinion on Drug Metabolism and Toxicology

Volumn 4, Issue 6, 2008, Pages 733-747

  Urban, Philippe ^a   Truan, Gilles ^a   Pompon, Denis ^a  

^a CENTRE DE GÉNÉTIQUE MOLÉCULAIRE   (France)

Author keywords

Combinatorial mutagenesis; Cytochromes P450; Drug development; Functional prediction; Multivariate analysis; Structure activity relationships

Indexed keywords

CYTOCHROME P450; CYTOCHROME P450 1A; FLAVONOID; MIFEPRISTONE; MOLECULAR SCAFFOLD; PRASTERONE; PROGESTERONE; STEROID; TERPENOID DERIVATIVE; TESTOSTERONE; XENOBIOTIC AGENT; CYTOCHROME P450 1A1; DRUG;

ANTINEOPLASTIC ACTIVITY; CATALYSIS; CHEMICAL STRUCTURE; COMBINATORIAL LIBRARY; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYMOLOGY; EXPERIMENTAL MODEL; HIGH THROUGHPUT SCREENING; HUMAN; MATHEMATICAL MODEL; MULTIVARIATE ANALYSIS; NONHUMAN; PROTEIN EXPRESSION; PROTEIN INTERACTION; REVIEW; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; AMINO ACID SEQUENCE; ANIMAL; BIOTRANSFORMATION; CHEMISTRY; COMBINATORIAL CHEMISTRY; COMPUTER SIMULATION; GENETICS; KINETICS; METABOLISM; MOLECULAR GENETICS; PROTEIN CONFORMATION; STATISTICAL MODEL;

AMINO ACID SEQUENCE; ANIMALS; BIOTRANSFORMATION; COMBINATORIAL CHEMISTRY TECHNIQUES; COMPUTER SIMULATION; CYTOCHROME P-450 CYP1A1; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; KINETICS; MODELS, MOLECULAR; MODELS, STATISTICAL; MOLECULAR SEQUENCE DATA; MOLECULAR STRUCTURE; MUTAGENESIS, SITE-DIRECTED; PHARMACEUTICAL PREPARATIONS; PROTEIN CONFORMATION; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 48949117165     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.4.6.733     Document Type: Review

References (99)

1. Roberts RJ. Identifying protein function: a call for community action. PLoS Biol 2004;2:e42
2. Fisher E. Einfluss der configuration auf die wirkung der enzyme. Chem Ber 1894;27:2985-93
3. Koshland DE Jr. Correlation of structure and function in enzyme action. Science 1963;142:1533-41
4. Miller SP, Lunzer M, Dean M. Direct demonstration of an adaptative constraint. Science 2006;314:458-61
5. Supuran CT. Carbonic anhydrases as drug targets: an overview. Curr Top Med Chem 2007;7:825-33
6. Verpoorte JA, Mehta S, Edsall JT. Esterase activities of human carbonic anhydrases B and C. J Biol Chem 1967;242:4221-9
7. Hult K, Berglund P. Enzyme promiscuity: mechanism and applications. 2007;25:231-8
8. Barglow KT, Cravitt BF. Activity-based protein profiling for the functional annotation of enzymes. Nat Methods 2007;4:822-7
9. Tang W, Wang RW, Lu AY. Utility of recombinant cytochromes P450 enzymes: a drug metabolism perspective. Curr Drug Metab 2005;6:503-17
10. Gillam EM, Guengerich FP. Exploiting the versatility of human cytochromes P450 enzymes: the promise of blue roses from biotechnology. IUMB Life 2001;52:271-7
11. Guengerich FP, Wu ZL, Bartleson CJ. Function of human cytochromes P450s: characterization of the orphans. Biochem Biophys Res Commun 2005;338:465-9
12. Shuler MA, Werck-Reichhart D. Functional genomics of P450s. Ann Rev Plant Biol 2003;54:629-67
13. Coon MJ. Cytochrome P450: nature's most versatile biological catalyst. Ann Rev Pharmacol Toxicol 2005;45:1-25
14. Lewis DF, Dickins M, Eddershaw PJ, et al. Cytochrome P450 substrate specificities, substrate structural templates and enzyme active site geometries. Drug Metabol Drug Interact 1999;15:1-49
15. Guengerich FP. Cytochrome P450 enzymes in the generation of commercial products. Nature Rev Drug Discov 2002;1:359-66
16. Waring JF, Ulrich RG. The impact of genomic-based technologies on drug safety evaluation. Ann Rev Pharmacol Toxicol 2000;40:335-52
17. Singh SS. Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr Drug Metab 2006;7:165-82
18. Aharoni A, Gaidukov L, Khersonsky O, et al. The evolvability of promiscuous protein functions. Nature Gen 2005;37:73-6
19. Khersonsky O, Roodveldt C, Tawfik DS. Enzyme promiscuity: evolutionary and mechanistic aspects. Curr Opin Chem Biol 2006;10:498-508
20. Petsko GA. Design by necessity. Nature 2000;403:606-7
21. Morley KL, Kazlauskas RJ. Improving enzyme properties: when are closer mutations better? Trends Biotech 2005;23:231-7
22. Nath A, Atkins WM. A quantitative index of substrate promiscuity. Biochemistry 2008;47:157-66
23. Carbone MN, Arnold FH. Engineering by homologous recombination: exploring sequence and function within a conserved fold. Curr Opin Struct Biol 2007;17:454-9
24. Lewis DFV. Human P450s in the metabolism of drugs: molecular modelling of enzyme-substrate interactions. Expert Opin Drug Metab Toxicol 2005;1:5-8
25. Nelson DR. Cytochrome P450 nomenclature. Methods Mol Biol 2006;320:1-10
26. Nelson DR. Available from: http://drnelson.utmem.edu/CytochromeP450.html Last access: Feb 20, 2008)
27. Guengerich FP. Cytochromes P450, drugs, and diseases. Mol Interv 2003;3:194-204
28. Johnson EF, Stout CD. Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem Biophys Res Commun 2005;338:331-6
29. Otyepka M, Skopalik J, Anzenbacherova E, Anzenbacher P. What common structural features and variations of mammalian P450s are known to date? Biochim Biophys Acta 2007;1770:376-89
30. Perret A, Pompon D. Electron shuttle between membrane-bound cytochromes P450 3A4 and b5 rules uncoupling mechanisms. Biochemistry 1998;37:11412-24
31. Urban P, Werck-Reichhart D, Teutsch HG, et al. Characterization of recombinant plant cinnamate 4-hydroxylase produced in yeast: kinetic and spectral properties of the major plant P450 of the phenylpropanoid pathway. Eur J Biochem 1994;222:843-50
32. Cojocaru V, Winn PJ, Wade RC. The ins and outs of cytochromes P450. Biochim Biophys Acta 2007;770:390-401
33. Taly V, Urban P, Truan G, Pompon D. A combinatorial approach to susbtrate discrimination in the P450 CYP1A subfamily. Biochim Biophys Acta 2007;1770:446-57
34. Scott EE, Halpert JR. Structures of cytochrome P450 3A4. Trends Biochem Sci 2005;30:5-7
35. Guengerich FP. A malleable catalyst dominates the metabolism of drugs. Proc Natl Acad Sci USA 2006;103:13565-6
36. Ekroos M, Sjögren T. Structural basis for ligand promiscuity in cytochrome P450 3A4. Proc Natl Acad Sci USA 2006;103:13682-7
37. Torimoto N, Ishii I, Toyama K, et al. Helices F-G are important for the substrate specilicities of CYP3A7. Drug Metab Dispos 2007;35:484-92
38. Bloom JD, Meyer MM, Meinhold P, et al. Evolving strategies for enzyme engineering. Curr Opin Struct Biol 2005;14:447-52
39. Joern JJ, Meinhold P, Arnold FH. Analysis of shuffled gene libraries. J Mol Biol 2002;316:643-56
40. Hiraga K, Arnold FH. General method for sequence independent site-directed chimeragenesis. J Mol Biol 2003;330:287-96
41. Otey CR, Landwher M, Endelman JB, et al. Structure-guided recombination creates an artificial family of cytochromes P450. PLoS Biol 2006;4:e112
42. Meyer MM, Silberg JJ, Voigt CA, et al. Library analysis of SCHEMA-guided protein recombinadon. Protein Sci 2003;12:1686-93
43. Pompon D, Nicolas A. Protein engineering by cDNA recombination in yeast: shuffling of mammalian cytochromes P450 functions. Gene 1989;83:15-24
44. Sakaki T, Shibata M, Yabusaki Y, Ohkawa H. Expression in Saccharomyces cerevisiae of chimeric cytochromes P450 cDNAs constructed from cDNAs for rat cytochromes P450s and P450d. DNA (NewYork) 1987;6:31-9
45. Mézard C, Pompon D, Nicolas A. Recombination between similar but not identical DNA sequences during yeast transformation occurs within short stretches of identity. Cell 1992;70:659-70
46. Kronbach T, Larabee TM, Johnson EF. Hybrid cytochromes P450 identify a substrate binding domain in P450 2C5 and P450 2C4. Proc Natl Acad Sci USA 1989;86:8262-5
47. Uno T, Imai Y. Further studies on chimeric P450 2C2-2C14 having testosterone 16-hydroxylase activity which is absent in the parental P450s. J Biochem (Tokyo) 1992;112:155-62
48. Johnson EF, Kronbach T, Hsu MH. Analysis of the catalytic specificity of cytochrome P450 enzymes through site-directed mutagenesis. FASEB J 1992;6:700-5
49. Brock BJ, Waterman MR. The use of random chimeragenesis to study structure-function properties of rat and human P450c17. Arch Biochem Biophys 2000;373:401-8
50. Fraser DJ, He YQ, Harlow GR, Halpert JR. Use of chimeric enzymes and site-directed mutagenesis for identification of three key residues responsible for differences in steroid hydroxylation between canine cytochromes P-450 3A12 and 3A26. Mol Pharmacol 1999;55:241-7
51. Otey CR, Silberg JJ, Voigt CA, et al. Functional evolution and structural conservation in chimeric cytochromes P450: calibrating a structure-guided approach. Chem Biol 2004;11:309-18
52. Shimada T, Murayama N, Okada K, et al. Different mechanisms for inhibition of human cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic inhibitors. Chem Res Toxicol 2007;20:489-96
53. Kimura S, Gonzalez FJ, Nebert DW. Tissue-specific expression of the mouse dioxin-inducible P(1)450 and P(3)450 genes: differential transcriptional activation and mRNA stability in liver and extrahepatic tissues. Mol Cell Biol 1986;6:1471-7 54 Ioannides C, Parke DV. The cytochromes P450 I gene family of microsomal hemoproteins and their role in the metabolic activation of chemicals. Drug Metab Rev 1990:22:1-85
54. Kim D, Guengerich FP. Cytochrome P450 activation of arylamines and heterocyclic amines. Ann Rev Pharmacol Toxical 2005;45:27-49
55. Pineau T, Fernandez-Salguera P, Lee SST, et al. Neonatal lethality associated with respiratory distress in mice lacking cytochrome P450 1A2. Proc Natl Acad Sci USA 1995;92:5134-8
56. Orr-Weaver TL, Szostak JW. Yeast recombination: the association between double-strand gap repair and crossing-over. Proc Natl Acad Sci USA 1983;80:4417-21
57. Abecassis V, Pompon D, Truan G. High efficiency family shuffling based on multi-step PCR and in vivo DNA recombination in yeast: statistical and functional analysis of a combinatorial library between human cytochromes P450 1A1 and 1A2. Nucleic Acids Res 2000;28:e88
58. Pompon D, Lauerat B, Bronine A, Urban P. Yeast expression of animal and plant P450s in optimized redox environments. Methods Enzymol 1996;272:51-64
59. Shimada T. Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons. Drug Metab Pharmacokinet 2006;21:257-76
60. Li Y, Fang H, Xu W. Recent advance in the research of flavonoids as anticancer agents. Mini Rev Med Chem 2007;7:663-78
61. Goddard JP, Reymond JL. Enzyme assays for high-throughput screening. Curr Opin Biotech 2004;15:314-22
62. White RE. High-throughput screening in drug metabolism and pharmacokinetic support of drug discovery. Ann Rev Pharmacol Toxicol 2000;40:133-57
63. Lee MY, Dordick JS. High-throughput human metabolism and toxicity analysis. Cur Opin Biotech 2006:17:619-27
64. Ansede JH, Thakker DR. High-throughput screening for stability and inhibitory activity of compounds toward cytochromes P450-mediated metabolism. J Pharm Sci 2004;93:239-55
65. Mastrobattista E, Taly V, Chanudet E, et al. High-throughput screening of enzyme libraries: in vitro evolution of a β-galactosidase by fluorescence-activated sorting of double emulsions. Chem Biol 2005;12:1291-300
66. Guarino RD, Dike LE, Haq TA, et al. Method for determining oxygen consumption rates of static cultures from microplate measurements of pericellular dissolved oxygen concentration. Biotechnol Bioeng 2004;86:775-87
67. Olry A, Schneider-Belhaddad F, Heintz D, Werck-Reichhart D. A medium-throughput screening assay to determine catalytic activities of oxygen-consuming enzymes: a new tool for functional characterization of cytochrome P450 and other oxygenases. Plant J 2007;51:331-40
68. Wu J, Hughes CS, Picard P, et al. High-throughput cytochrome P450 inhibition assays using laser diode thermal desorption-APCI-tandem mass spectrometry. Anal Chem 2007;79:4657-65
69. Fisher RA. The correlation between relatives on the supposition of Mendelian inheritance. Phil Transac Roy Sac 1918;52:399-433
70. Larsson AK, Emren LO, Barsdley WG, Mannervik B. Directed enzyme evolution guided by multidimensional analysis of substrate-activity space. Protein Eng Des Select 2004;17:49-55
71. Emren LO, Kurtovic S, Runarsdottir A, et al. Functionally divergent molecular quasi-species evolve by crossing two enzymes. Proc Natl Acad Sci USA 2006;103:10866-70
72. Eigen M, McCaskill J, Schuster P. Molecular quasi-species. J Phys Chem 1988;92:6881-91
73. Biebricher CK, Eigen NM. What is a quasi-species? Curr Top Microbiol Immunol 2006;299:1-31
74. Kurtovic S, Runarsdottir A, Emren LO, et al. Multivariate-activity mining for molecular quasi-species in a glutathione transferase mutant library. Protein Eng Des Sel 2007;20:243-56
75. Joo H, Lin Z, Arnold FH. Laboratory evolution of peroxide-mediated cytochromes P450 hydroxylation. Nature 1999;399:670-3
76. Glieder A, Farinas ET, Arnold FH. Laboratory evolution of a soluble, self-sufficient, highly active alkane hydroxylase. Nat Biotechnol 2002;20:1135-9
77. Peters MW, Meinhold P, Glieder A, Arnold FH. Regio- and enantio-selective alkane production with engineered cytochromes P450 BM3. J Am Chem Soc 2003;125:13442-50
78. Van Vugt-Lussenburg BMA, Stjernschantz E, Lastdrager J, et al. Identification of critical residues in novel drug metabolizing mutants of cytochromes P450 BM3 using random mutagenesis. J Med Chem 2007;50:455-61
79. Li Y, Drummond DA, Sawayama AM, et al. A diverse family of thermostable cytochromes P450 created by recombination of stabilizing fragments. Nat Biotechnol 2007;25:1051-6
80. Johnston WA, Huang W, De Voss JJ, et al. A shuffled CYP1A library shows both structural integrity and functional diversity. Drug Metab Dispos 2007;35:2177-85
81. Kumar S, Chen CS, Waxman DJ, Halpert JR. 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 2005;280:19569-75
82. Kumar S, Sun L, Liu H, et al. Engineering mammalian cytochrome P450 2B1 by directed evolution for enhanced catalytic tolerance to temperature and dimethyl sulfoxide. Protein Eng Des Sel 2006;19:547-54
83. Zhao Y, Halpert JR. Structure-function analysis of cytochromes P450 2B. Biochim Biophys Acta 2007;1770:402-12
84. Huang W, Johnston WA, Hayes MA, et al. A shuffled CYP2C library with a high degree of structural integrity and functional versatility. Arch Biochem Biophys 2007;467:193-205
85. Kumar S, Liu H, Halpert JR. Engineering of cytochrome P450 3A4 for enhanced peroxide-mediated substrate oxidation using directed evolution and site-directed mutagenesis. Drug Metab Dispos 2006;34:1958-65
86. Parikh A, Josephy PD, Guengerich FP. Selection and characterization of human cytochromes P450 1A2 mutants with altered catalytic properties. Biochemistry 1999;38:5283-9
87. Kim D, Guengerich FP. Enhancement of 7-methoxyresorufin O-demethylation activity of human cytochromes P450 1A2 by molecular breeding. Arch Biochem Biophys 2004;346:269-76
88. Kim D, Guengerich FP. Selection of human cytochromes P450 1A2 mutants with enhanced catalytic activity for heterocyclic amine N-hydroxylation. Biochemistry 2004;43:981-8
89. Coxon APM. A user's guide to multidimensional scaling. London: Heineman Educational Books; 1982
90. Pearson K. On lines and planes of closest fit to systems of points in space. Phil Magas 1901;2:559-72
91. Jackson JE. A user's guide to principal components. New York Wiley; 1991
92. Sansen S, Yano JK, Reynald RL, et al. Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem 2007;282:14348-55
93. Wang J, Urban L, Bojanic D. Maximising use of in vitro ADMET tools to predict in vivo bioavailability and safety. Expert Opin Drug Metab Toxicol 2007;3:641-65
94. Kenworthy KE, Bloomer JC, Clarke SE, Houston JB. CYP3A4 drug interactions: correlation of ten in vitro probe substrates. Br J Clin Pharmacol 1999;48:716-27
95. Landwehr M, Carbone M, Otey CR, et al. Diversification of catalytic function in a synthetic family of chimeric cytochromes P450. Chem Biol 2007;14:269-78
96. Blundell TL, Patel S. High-throughput X-ray crystallography for drug discovery. Curr Opin Pharm 2004;4:490-6
97. Prasad JC, Goldstone JV, Camacho CJ, et al. Ensemble modelling of substrate binding to cytochromes P450: analysis of catalytic differences between CYP1A orthologs. Biochemistry 2007;46:2640-54
98. Fox RJ, Davis SC, Mundorff EC, et al. Improving catalytic function by ProSAR-driven enzyme evolution. Nat Biotechnol 2007;25:338-44
99. Fox RJ, Huisman GW. Enzyme optimization: moving from blind evolution to statistical exploration of sequence-function space. Trends Biotechnol 2008;26:132-8