Identification of critical residues in novel drug metabolizing mutants of cytochrome P450 BM3 using random mutagenesis

Journal of Medicinal Chemistry

Volumn 50, Issue 3, 2007, Pages 455-461

  Van Vugt Lussenburg, Barbara M A ^a   Stjernschantz, Eva ^a   Lastdrager, Jeroen ^a   Oostenbrink, Chris ^a   Vermeulen, Nico P E ^a   Commandeur, Jan N M ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

3,4 METHYLENEDIOXYMETHAMPHETAMINE; CYTOCHROME P450 2D6; CYTOCHROME P450 BM3; DEXTROMETHORPHAN; DRUG METABOLIZING ENZYME; MUTANT PROTEIN;

ARTICLE; COMPUTER MODEL; DRUG METABOLISM; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME SUBSTRATE; MUTAGENESIS; SATURATION MUTAGENESIS; SEQUENCE ANALYSIS; SITE DIRECTED MUTAGENESIS;

BACTERIAL PROTEINS; BINDING SITES; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; DEXTROMETHORPHAN; HUMANS; KINETICS; MIXED FUNCTION OXYGENASES; MODELS, MOLECULAR; MUTAGENESIS; MUTATION; N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; OXAZINES; SEQUENCE ANALYSIS, DNA;

EID: 33846931755     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0609061     Document Type: Article

References (34)

1. van Vugt-Lussenburg, B. M. A.; Damsten, M. C.; Maasdijk, D. M.; Vermeulen, N. P. E.; Commandeur, J. N. M. Heterotropic and homotropic cooperativity by a drug-metabolising mutant of cytochrome P450 BM3. Biochem. Biophys. Res. Commun. 2006, 346, 810-818.
2. Guengerich, F. P. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 2001, 14, 611-650.
3. Guengerich, F. P. Cytochrome P450 enzymes in the generation of commercial products. Nat. Rev. Drug. Discovery 2002, 1, 359-366.
4. Urlacher, V. B.; Lutz-Wahl, S.; Schmid, R. D. Microbial P450 enzymes in biotechnology. Appl. Microbiol. Biotechnol. 2004, 64, 317-325.
5. Munro, A. W.; Leys, D. G.; McLean, K. J.; Marshall, K. R.; Ost, T. W.; Daff, S.; Miles, C. S.; Chapman, S. K.; Lysek, D. A.; Moser, C. C.; Page, C. C.; Dutton, P. L. P450 BM3: the very model of a modern flavocytochrome. Trends Biochem. Sci. 2002, 27, 250-257.
6. Urlacher, V.; Schmid, R. D. Biotransformations using prokaryotic P450 monooxygenases. Curr. Opin. Biotechnol. 2002, 13, 557-564.
7. Narhi, L. O.; Fulco, A. J. Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J. Biol. Chem. 1986, 261, 7160-7169.
8. Glieder, A.; Farinas, E. T.; Arnold, F. H. Laboratory evolution of a soluble, self-sufficient, highly active alkane hydroxylase. Nat. Biotechnol. 2002, 20, 1135-1139.
9. Li, Q. S.; Schwaneberg, U.; Fischer, P.; Schmid, R. D. Directed evolution of the fatty-acid hydroxylase P450 BM-3 into an indolehydroxylating catalyst. Chemistry 2000, 6, 1531-1536.
10. Otey, C. R.; Bandara, G.; Lalonde, J.; Takahashi, K.; Arnold, F. H. Preparation of human metabolites of propranolol using laboratory-evolved bacterial cytochromes P450. Biotechnol. Bioeng. 2006, 93, 494-499.
11. Lussenburg, B. M. A.; Babel, L. C.; Vermeulen, N. P. E.; Commandeur, J. N. M. Evaluation of alkoxyresorufins as fluorescent substrates for cytochrome P450 BM3 and site-directed mutants. Anal. Biochem. 2005, 341, 148-155.
12. Noble, M. A.; Miles, C. S.; Chapman, S. K.; Lysek, D. A.; MacKay, A. C.; Reid, G. A.; Hanzlik, R. P.; Munro, A. W. Roles of key active-site residues in flavocytochrome P450 BM3. Biochem. J. 1999, 339 (Pt 2), 371-379.
13. Keizers, P. H. J.; Lussenburg, B. M. A.; de Graaf, C.; Mentink, L. M.; Vermeulen, N. P. E.; Commandeur, J. N. M. Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism. Biochem. Pharmacol. 2004, 68, 2263-2271.
14. Li, Q. S.; Ogawa, J.; Schmid, R. D.; Shimizu, S. Engineering cytochrome P450 BM-3 for oxidation of polycyclic aromatic hydrocarbons. Appl. Environ. Microbiol. 2001, 67, 5735-5739.
15. Haines, D. C.; Tomchick, D. R.; Machius, M.; Peterson, J. A. Pivotal role of water in the mechanism of P450BM-3. Biochemistry 2001, 40, 13456-13465.
16. Sevrioukova, I. F.; Li, H.; Zhang, H.; Peterson, J. A.; Poulos, T. L. Structure of a cytochrome P450-redox partner electron-transfer complex. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 1863-1868.
17. Kumar, S.; Halpert, J. R. Use of directed evolution of mammalian cytochromes P450 for investigating the molecular basis of enzyme function and generating novel biocatalysts. Biochem. Biophys. Res. Commun. 2005, 338, 456-464.
18. Straathof, A. J.; Panke, S.; Schmid, A. The production of fine chemicals by biotransformations. Curr. Opin. Biotechnol. 2002, 13, 548-556.
19. Wen, Z.; Baudry, J.; Berenbaum, M. R.; Schuler, M. A. Ile115Leu mutation in the SRS1 region of an insect cytochrome P450 (CYP6B1) compromises substrate turnover via changes in a predicted product release channel. Protein Eng. Des. Sel. 2005, 18, 191-199.
20. Yeom, H.; Sligar, S. G. Oxygen activation by cytochrome P450BM-3: effects of mutating an active site acidic residue. Arch. Biochem. Biophys. 1997, 337, 209-216.
21. Guenther, M. G.; Witmer, M. R.; Burke, J. R. Cytosolic phospholipase A2 shows burst kinetics consistent with the slow, reversible formation of a dead-end complex. Arch. Biochem. Biophys. 2002, 398, 101-108.
22. Farinas, E.; Schwaneberg, U.; Glieder, A.; Arnold, F. H. Directed evolution of a Cytochrome P450 Monooxygenase for Alkane Oxidation. Adv. Synth. Catal. 2001, 343, 601-606.
23. Bauer, S.; Shiloach. J. Maximal exponential growth rate and yield of E. coli obtainable in a bench-scale fermentor. Biotechnol. Bioeng. 1974, 16, 933-941.
24. Lussenburg, B. M. A.; Keizers, P. H. J.; de Graaf, C.; Hidestrand, M.; Ingelman-Sundberg, M.; Vermeulen, N. P. E.; Commandeur, J. N. M. The role of phenylalanine 483 in cytochrome P450 2D6 is strongly substrate dependent. Biochem. Pharmacol. 2005, 70, 1253-1261.
25. MOE, Chemical Computing Group Inc.: Montreal, Quebec, Canada.
26. Jones, G.; Willett, P.; Glen, R. C.; Leach, A. R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol. 1997, 267, 727-748.
27. Christen, M.; Hunenberger, P. H.; Bakowies, D.; Baron, R.; Burgi, R.; Geerke, D. P.; Heinz, T. N.; Kastenholz, M. A.; Krautler, V.; Oostenbrink, C.; Peter, C.; Trzesniak, D.; van Gunsteren, W. F. The GROMOS software for bioMol. Simul.: GROMOS05. J. Comput. Chem. 2005, 26, 1719-1751.
28. Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R. GRO-MACS: A message-passing parallel molecular dynamics implementation. Comp. Phys. Commun. 1995, 91, 43-56.
29. Lindahl, E.; Hess, B.; van der Spoel, D. GROMACS 3.0: A package for Molecular Simulation and trajectory analysis. J. Mol. Mod. 2001, 7, 306-317.
30. Schuler, L. D.; Daura, X.; van Gunsteren, W. F. An improved GROMOS96 force field for aliphatic hydrocarbons in the condensed phase. J. Comput. Chem. 2001, 22, 1205-1218.
31. van Gunsteren, W. F.; Billeter, S. R.; Eising, A. A.; Hunenberger, P. H.; Kruger, P.; Mark, A. E.; Scott, W. R. P.; Tironi, I. G. Biomolecular Simulation: The GROMOS96 manual and user guide; Vdf Hochschulverlag AG an der ETH Zurich: Zurich, 1996.
32. Keizers, P. H. J.; de Graaf, C.; de Kanter, F. J.; Oostenbrink, C.; Feenstra, K. A.; Commandeur, J. N. M.; Vermeulen, N. P. E. Metabolic regio- and stereoselectivity of cytochrome P450 2D6 towards 3,4-methylenedioxy-N- alkylamphetamines: in silico predictions and experimental validation. J. Med. Chem. 2005, 48, 6117-6127.
33. Tew, D. G. Inhibition of cytochrome P450 reductase by the diphenyliodonium cation. Kinetic analysis and covalent modifications. Biochemistry 1993, 32, 10209-10215.
34. Note: the equation described by Noble et al. contains a typographical error; one of the parentheses is misplaced.