Production of human phase 1 and 2 metabolites by whole-cell biotransformation with recombinant microbes

Bioanalysis

Volumn 2, Issue 7, 2010, Pages 1277-1290

  Zöllner, Andy ^a   Buchheit, Daniela ^a   Meyer, Markus R ^b   Maurer, Hans H ^b   Peters, Frank T ^c   Bureik, Matthias ^a  

^a PomBioTech GmbH   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

^c FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL DEHYDROGENASE; ALDEHYDE DEHYDROGENASE; AMINE OXIDASE (FLAVIN CONTAINING); CYTOCHROME P450 1A2; CYTOCHROME P450 BM3; EPOXIDE HYDROLASE; GLUCURONIDE; GLUCURONOSYLTRANSFERASE 1A1; GLUCURONOSYLTRANSFERASE 1A4; UNSPECIFIC MONOOXYGENASE; ENZYME; RECOMBINANT DNA;

BIOCATALYSIS; CELL TRANSFORMATION; ENZYME ACTIVITY; ENZYME LOCALIZATION; ENZYME SYNTHESIS; ESCHERICHIA COLI; HUMAN; IN VITRO STUDY; INTERMETHOD COMPARISON; LIVER MICROSOME; METABOLITE; NONHUMAN; PICHIA PASTORIS; PROTEIN EXPRESSION; REVIEW; SACCHAROMYCES CEREVISIAE; SCHIZOSACCHAROMYCES POMBE; SPECIES DIFFERENCE; WHOLE CELL; ANIMAL; BIOSYNTHESIS; DRUG DETOXIFICATION; GENETIC ENGINEERING; GENETICS; ISOLATION AND PURIFICATION; METABOLISM; METHODOLOGY; MICROBIOLOGY;

ANIMALS; DNA, RECOMBINANT; ENZYMES; GENETIC ENGINEERING; HUMANS; METABOLIC DETOXICATION, PHASE I; METABOLIC DETOXICATION, PHASE II; MICROBIOLOGY;

EID: 79952470677     PISSN: 17576180     EISSN: 17576199     Source Type: Journal    
DOI: 10.4155/bio.10.80     Document Type: Review

References (132)

1. Thompson TN. Safety testing of drug metabolites. In:Annual Reports in Medicinal Chemistry . Macor JE (Ed.).Academic Press, London, UK (2009).
2. Davis-Bruno Kl, Atrakchi A. A regulatory perspective on issues and approaches in characterizing human metabolites. Chem. Res. Toxicol. 19(12), 1561-1563 (2006). (Pubitemid 44975118)
3. US FDA. Guidance for industry: safety testing of drug metabolites. (2008).
4. Bernhardt R. Cytochrome P450: structure, function, and generation of reactive oxygen species. Rev. Physiol. Biochem. Pharmacol. 127, 137-221 (1996).
5. Bernhardt R. Cytochromes P450 as versatile biocatalysts. J. Biotechnol. 124(1), 128-145. (2006). (Pubitemid 43816140)
6. Guengerich FP. Cytochrome P450: what have we learned and what are the future issues? Drug Metab. Rev. 36(2), 159-197 (2004). (Pubitemid 38802485)
7. Hannemann F, Bichet A, Ewen KM, Bernhardt R. Cytochrome P450 systems-biological variations of electron transport chains. Biochim. Biophys. Acta 1770(3), 330-344 (2006).
8. Nebert DW, Dalton TP. The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat. Rev. Cancer 6(12), 947-960 (2006). (Pubitemid 44862679)
9. Omura T, Sato R. A new cytochrome in liver microsomes. J. Biol. Chem. 237, 1375-1376 (1962).
10. Stark K, Guengerich FP. Characterization of orphan human cytochromes P450. Drug Metab. Rev. 39(2-3), 627-637 (2007). (Pubitemid 47355742)
11. Julsing MK, Cornelissen S, Buhler B, Schmid A. Heme-iron oxygenases: powerful industrial biocatalysts? Curr. Opin. Chem. Biol. 12(2), 177-186 (2008).
12. 5 in bacterial membranes. Drug Metab. Dispos. 27(9), 999-1004 (1999). (Pubitemid 29409634)
13. Vail RB, Homann MJ, Hanna I, Zaks A. Preparative synthesis of drug metabolites using human cytochrome P450S 3A4, 2C9 and 1A2 with NADPH-P450 reductase expressed in Escherichia coli. J. Ind. Microbiol. Biotechnol. 32(2), 67-74 (2005). (Pubitemid 40558570)
14. Kolar NW, Swart AC, Mason JI, Swart P. Functional expression and characterisation of human cytochrome P45017 α in Pichia pastoris. J. Biotechnol. 129(4), 635-644 (2007). (Pubitemid 46590451)
15. Soars MG, Mcginnity DF, Grime K, Riley RJ. The pivotal role of hepatocytes in drug discovery. Chem. Biol. Interact. 168(1), 2-15 (2007). (Pubitemid 46661937)
16. Gonzalez FJ, Crespi CL, Gelboin HV. DNA-expressed human cytochrome P450s: a new age of molecular toxicology and human risk assessment. Mutat. Res. 247(1), 113-127 (1991).
17. Buters JT, Korzekwa KR, Kunze KL, Omata Y, Hardwick JP, Gonzalez FJ. CDNA-directed expression of human cytochrome p450 CYP3A4 using baculovirus. Drug Metab. Dispos. 22(5), 688-692 (1994). (Pubitemid 24307481)
18. Peters FT, Bureik M, Maurer HH. Biotechnological synthesis of drug metabolites using human cytochrome P450 isozymes heterologously expressed in fission yeast. Bioanalysis 1(4), 821-830 (2009).
19. 5. Arch. Biochem. Biophys. 348(1), 107-115 (1997). (Pubitemid 27514676)
20. Guengerich FP. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14(6), 611-650 (2001). (Pubitemid 32565712)
21. Kim DH, Kim KH, Isin EM et al. Heterologous expression and characterization of wild-type human cytochrome P450 1A2 without conventional N-terminal modification in Escherichia coli. Protein Expr. Purif. 57(2), 188-200 (2008). (Pubitemid 350296980)
22. Zmijewski M, Gillespie TA, Jackson DA, Schmidt DF, Yi P, Kulanthaivel P. Application of biocatalysis to drug metabolism: preparation of mammalian metabolites of a biaryl-bis-sulfonamide AMPA (α-amino-3-hydroxy-5- methylisoxazole-4-propionic acid) receptor potentiator using actinoplanes missouriensis. Drug Metab. Dispos. 34(6), 925-931 (2006). (Pubitemid 43763746)
23. Yun CH, Yim SK, Kim DH, Ahn T. Functional expression of human cytochrome P450 enzymes in Escherichia coli. Curr. Drug Metab. 7(4), 411-429 (2006).
24. Van Beilen JB, Holtackers R, Luscher D, Bauer U, Witholt B, Duetz WA. Biocatalytic production of perillyl alcohol from limonene by using a novel Mycobacterium sp cytochrome P450 alkane hydroxylase expressed in Pseudomonas putida. Appl. Environ. Microbiol. 71(4), 1737-1744 (2005). (Pubitemid 40546088)
25. Fujita K, Kamataki T. Role of human cytochrome P450 (CYP) in the metabolic activation of N-alkylnitrosamines: application of genetically engineered Salmonella typhimurium YG7108 expressing each form of CYP together with human NADPH-cytochrome P450 reductase. Mutat. Res. Fund. Mol. Mech. Mut. 483(1-2), 35-41 (2001). (Pubitemid 33000063)
26. Rushmore TH, Reider PJ, Slaughter D, Assang C, Shou M. Bioreactor systems in drug metabolism: synthesis of cytochrome P450-generated metabolites. Metab. Eng. 2(2), 115-125 (2000). (Pubitemid 30416584)
27. Harnastai IN, Gilep AA, Usanov SA. The development of an efficient system for heterologous expression of cytochrome P450s in Escherichia coli using heme gene coexpression. Protein Expr. Purif. 46(1), 47-55 (2006). (Pubitemid 43246995)
28. Uchida E, Kagawa N, Sakaki T et al. Purification and characterization of mouse CYP27B1 overproduced by an Escherichia coli system coexpressing molecular chaperonins GROEL/ES. Biochem. Biophys. Res. Commun. 323(2), 505-511 (2004). (Pubitemid 39221126)
29. Zollner A, Kagawa N, Waterman MR et al. Purification and functional characterization of human 11ß hydroxylase expressed in Escherichia coli. FEBS J. 275(4), 799-810 (2008). (Pubitemid 351160976)
30. Narhi LO, Fulco AJ. Identification and characterization of two functional domains in cytochrome P-450BM-3, a catalytically self-sufficient monooxygenase induced by barbiturates in Bacillus megaterium. J. Biol. Chem. 262(14), 6683-6690 (1987).
31. Noble MA, Miles CS, Chapman SK et al. Roles of key active-site residues in flavocytochrome P450 BM3. Biochem. J. 339, 371-379 (1999). (Pubitemid 29209968)
32. Otey CR, Bandara G, Lalonde J, Takahashi K, Arnold FH. Preparation of human metabolites of propranolol using laboratory-evolved bacterial cytochromes P450. Biotechnol. Bioeng. 93(3), 494-499 (2006). (Pubitemid 43232175)
33. Schwaneberg U, Otey C, Cirino PC, Farinas E, Arnold FH. Cost-effective whole-cell assay for laboratory evolution of hydroxylases in Escherichia coli. J. Biomol. Screen 6(2), 111-117 (2001). (Pubitemid 32373802)
34. Hamann T, Moller BL. Improved cloning and expression of cytochrome P450s and cytochrome P450 reductase in yeast. Protein Expr. Purif. 56(1), 121-127 (2007). (Pubitemid 47505315)
35. Bureik M, Schiffler B, Hiraoka Y, Vogel F, Bernhardt R. Functional expression of human mitochondrial CYP11B2 in fission yeast and identification of a new internal electron transfer protein, etp1. Biochemistry 41(7), 2311-2321 (2002). (Pubitemid 34160893)
36. 5. Eur. J. Biochem. 207(1), 109-116 (1992).
37. Goffeau A, Barrell BG, Bussey H et al. Life with 6000 genes. Science 274(5287), 546, 563-7 (1996).
38. De Schutter K, Lin YC, Tiels P et al. Genome sequence of the recombinant protein production host Pichia pastoris. Nat. Biotechnol. 27(6), 561-566 (2009).
39. Alfa C, Fantes P, Hyams J, Mcleod M, Warbrick E. Experiments with Fission Yeast. A laboratory Course Manual. Cold Spring Harbor Press, Cold Spring Harbor, NY, USA (1993).
40. Sambrook J, Rusell DW. Molecular Cloning: A Laboratory Manual. CSHL Press, Woodbury, NY, USA (2001).
41. Cereghino JL, Cregg JM. Heterologous protein expression in the methylotrophic yeast Pichia pastoris. FEMS Microbiol Rev. 24(1), 45-66 (2000). (Pubitemid 30047114)
42. Cereghino GPL, Cereghino JL, Ilgen C, Cregg JM. Production of recombinant proteins in fermenter cultures of the yeast Pichia pastoris. Curr. Opin. Biotechnol. 13(4), 329-332 (2002). (Pubitemid 35254090)
43. Peters FT, Dragan CA, Wilde DR et al. Biotechnological synthesis of drug metabolites using human cytochrome P450 2D6 heterologously expressed in fission yeast exemplified for the designer drug metabolite 4́-hydroxymethyl- α-pyrrolidinobutyrophenone. Biochem. Pharmacol. 74(3), 511-520 (2007). (Pubitemid 46963243)
44. Peters FT, Dragan CA, Schwaninger AE et al. Use of fission yeast heterologously expressing human cytochrome P450 2B6 in biotechnological synthesis of the designer drug metabolite N-(1-phenylcyclohexyl)-2- hydroxyethanamine. Forensic Sci. Int. 184, 69-73 (2009).
45. Dumas B, Pompon D, Chandelier F et al. Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Yeast 20, S220-S220 (2003).
46. Szczebara FM, Chandelier C, Villeret C et al. Total biosynthesis of hydrocortisone from a simple carbon source in yeast. Nat. Biotechnol. 21(2), 143-149 (2003). (Pubitemid 36188212)
47. Dragan CA, Blank LM, Bureik M. Increased TCA cycle activity and reduced oxygen consumption during cytochrome P450- dependent biotransformation in fission yeast. Yeast 23(11), 779-794 (2006). (Pubitemid 44430579)
48. Dragan CA, Hartmann RW, Bureik M. A fission yeast based test system for the determination of IC50 values of antiprostate tumor drugs acting on cyp21. J. Enzyme Inhib. Med. Chem. 21(5), 547-556 (2006). (Pubitemid 44773215)
49. Dragan CA, Zearo S, Hannemann F, Bernhardt R, Bureik M. Efficient conversion of 11-deoxycortisol to cortisol (hydrocortisone) by recombinant fission yeast Schizosaccharomyces pombe. FEMS Yeast Res. 5, 621-625 (2005). (Pubitemid 40380701)
50. Peters FT, Dragan CA, Kauffels A et al. Biotechnological synthesis of the designer drug metabolite 4′-hydroxymethyl-α- pyrrolidinohexanophenone in fission yeast heterologously expressing human cytochrome P450 2D6-A versatile alternative to multistep chemical synthesis. J. Anal. Toxicol. 33(4), 190-197 (2009).
51. Zöllner A, Dragan CA, Pistorius D et al. Human CYP4Z1 catalyzes the in-chain hydroxylation of lauric acid and myristic acid. Biol. Chem. 390, 313-317 (2009).
52. Zollner A, Parr MK, Dragan CA et al. CYP21-catalyzed production of the long-term urinary metandienone metabolite 17ß-hydroxymethyl-17a-methyl-18- norandrosta-1,4,13-trien-3-one: a contribution to the fight against doping. Biol. Chem. 391(1), 119-127 (2010).
53. Peters FT, Schwaninger AE, Dragan CA, Bureik M, Maurer HH. New fission yeast strains expressing human cytochrome p450 enzymes to be used for biotechnological synthesis of drug metabolites. Ther. Drug. Monit. 29(4), 466-467 (2007).
54. Peters FT, Schwaninger AE, Sauer C et al. Isolation and purification of the designer drug metabolite O-desethyl-N-(1-phenylcyclohexyl)-3- ethoxypropanamine (O-desethyl-PCEPA) biotechnologically synthesized using fission yeast expressing CYP2D6. Presente at: XV. GTFCh-Symposium. Mosbach, Germany, 18-21 April 2007.
55. Iwata H, Fujita K, Kushida H et al. High catalytic activity of human cytochrome P450 coexpressed with human NADPH-cytochrome P450 reductase in Escherichia coli. Biochem. Pharmacol. 55(8), 1315-1325 (1998). (Pubitemid 28206722)
56. Blake JAR, Pritchard M, Ding SH et al. Coexpression of a human P450 (CYP3A4) and P450 reductase generates a highly functional monooxygenase system in Escherichia coli. FEBS Lett. 397(2-3), 210-214 (1996). (Pubitemid 26414019)
57. Chang MCY, Eachus RA, Trieu W, Ro DK, Keasling JD. Engineering Escherichia coli for production of functionalized terpenoids using plant P450s. Nat. Chem. Biol. 3(5), 274-277 (2007). (Pubitemid 46625834)
58. Hummel W. New alcohol dehydrogenases for the synthesis of chiral compounds. Adv. Biochem. Eng. Biotechnol. 58, 145-184 (1997).
59. Bronley-Delancey A, McMillan DC, McMillan JM, Jollow DJ, Mohr LC, Hoel DG. Application of cryopreserved human hepatocytes in trichloroethylene risk assessment: relative disposition of chloral hydrate to trichloroacetate and trichloroethanol. Environ. Health Perspect. 114(8), 1237-1242 (2006). (Pubitemid 44184683)
60. Griffin DR, Gainer JL, Carta G. Asymmetric ketone reduction with immobilized yeast in hexane: biocatalyst deactivation and regeneration. Biotechnol. Prog. 17(2), 304-310 (2001). (Pubitemid 32663395)
61. Yu MA, Wei YM, Zhao L, Jiang L, Zhu XB, Qi W. Bioconversion of ethyl 4-chloro-3- oxobutanoate by permeabilized fresh brewer's yeast cells in the presence of allyl bromide. J. Ind. Microbiol. Biotechnol. 34(2), 151-156 (2007). (Pubitemid 46147395)
62. Katzberg M, Wechler K, Muller M et al. Biocatalytical production of (5s)-hydroxy-2- hexanone. Org. Biomol. Chem. 7(2), 304-314 (2009).
63. Stampfer W, Kosjek B, Faber K, Kroutil W. Biocatalytic asymmetric hydrogen transfer employing Rhodococcus ruber DSM 44541. J. Org. Chem. 68(2), 402-406 (2003). (Pubitemid 36125972)
64. Stampfer W, Kosjek B, Kroutil W, Faber K. On the organic solvent and thermostability of the biocatalytic redox system of Rhodococcus ruber DSM 44541. Biotechnol. Bioeng. 81(7), 865-869 (2003). (Pubitemid 36313725)
65. Yamamoto H, Matsuyama A, Kobayashi Y. Synthesis of ethyl (R)-4-chloro-3- hydroxybutanoate with recombinant Escherichia coli cells expressing (S)-specific secondary alcohol dehydrogenase. Biosci. Biotechnol. Biochem. 66(2), 481-483 (2002). (Pubitemid 39251081)
66. Yamamoto H, Matsuyama A, Kobayashi Y. Synthesis of (R)-1,3-butanediol by enantioselective oxidation using whole recombinant Escherichia coli cells expressing (S)-specific secondary alcohol dehydrogenase. Biosci. Biotechnol. Biochem. 66(4), 925-927 (2002). (Pubitemid 39251368)
67. Ernst M, Kaup B, Muller M, Bringer-Meyer S, Sahm H. Enantioselective reduction of carbonyl compounds by whole-cell biotransformation, combining a formate dehydrogenase and a (R)-specific alcohol dehydrogenase. Appl. Microbiol. Biotechnol. 66(6), 629-634 (2005). (Pubitemid 40385625)
68. +-dependent formate dehydrogenase. Biotechnol. Lett. 26(22), 1739-1744 (2004). (Pubitemid 40141225)
69. Goldberg K, Edegger K, Kroutil W, Liese A. Overcoming the thermodynamic limitation in asymmetric hydrogen transfer reactions catalyzed by whole cells. Biotechnol. Bioeng. 95(1), 192-198 (2006). (Pubitemid 44342364)
70. Schroer K, Peter Luef K, Stefan Hartner F, Glieder A, Pscheidt B. Engineering the Pichia pastoris methanol oxidation pathway for improved NADH regeneration during whole-cell biotransformation. Metab. Eng. 12(1), 8-17 (2009).
71. Long A, Ward OP. Biotransformation of benzaldehyde by Saccharomyces cerevisiae: characterization of the fermentation and toxicity effects of substrates and products. Biotechnol. Bioeng. 34(7), 933-941 (1989). (Pubitemid 19235669)
72. Zocher F, Enzelberger MM, Bornscheuer UT, Hauer B, Wohlleben W, Schmid RD: Epoxide hydrolase activity of streptomyces strains. J. Biotechnol. 77(2-3), 287-292 (2000). (Pubitemid 30055343)
73. Li C, Liu Q, Song X, Di D, Ji A, Qu Y. Epoxide hydrolase-catalyzed resolution of ethyl 3-phenylglycidate using whole cells of Pseudomonas sp. Biotechnol. Lett. 25(24), 2113-2116 (2003). (Pubitemid 38092571)
74. Xu Y, Xu JH, Pan J, Tang YF. Biocatalytic resolution of glycidyl aryl ethers by Trichosporon loubierii: cell/substrate ratio influences the optical purity of (R)-epoxides. Biotechnol. Lett. 26(15), 1217-1221 (2004). (Pubitemid 40938273)
75. Kotik M, Brichac J, Kyslik P. Novel microbial epoxide hydrolases for biohydrolysis of glycidyl derivatives. J. Biotechnol. 120(4), 364-375 (2005). (Pubitemid 41627966)
76. Liu Y, Sha Q, Wu S, Wang J, Yang L, Sun W. Enzymatic resolution of racemic phenyloxirane by a novel epoxide hydrolase from Aspergillus niger SQ-6 and its fed-batch fermentation. J. Ind Microbiol. Biotechnol. 33(4), 274-282 (2006). (Pubitemid 43345192)
77. Labuschagne M, Albertyn J. Cloning of an epoxide hydrolase-encoding gene from Rhodotorula mucilaginosa and functional expression in yarrowia lipolytica. Yeast 24(2), 69-78 (2007). (Pubitemid 46322379)
78. Hwang YO, Kang SG, Woo JH et al. Screening enantioselective epoxide hydrolase activities from marine microorganisms: detection of activities in Erythrobacter spp. Mar. Biotechnol. 10(4), 366-373 (2008).
79. Phillips IR, Shephard EA. Flavin-containing monooxygenases: mutations, disease and drug response. Trends. Pharmacol. Sci. 29(6), 294-301 (2008).
80. Crettol S, Petrovic N, Murray M. Pharmacogenetics of phase I and phase II drug metabolism. Curr. Pharm. Des. 16(2), 204-219 (2010).
81. Iyanagi T. Molecular mechanism of phase I and phase II drug-metabolizing enzymes: implications for detoxification. Int. Rev. Cytol. 260, 35-112 (2007). (Pubitemid 46670211)
82. Williams JA, Hyland R, Jones BC et al. Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab. Dispos. 32(11), 1201-1208 (2004). (Pubitemid 39410902)
83. Mackenzie PI, Bock KW, Burchell B et al. Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet. Genomics 15(10), 677-685 (2005). (Pubitemid 41345319)
84. Tukey RH, Strassburg CP. Human UDP-glucuronosyltransferases: metabolism, expression, and disease. Annu. Rev. Pharmacol. Toxicol. 40, 581-616 (2000). (Pubitemid 30340694)
85. Bock KW, Köhle C. Topological aspects of oligomeric UDP-glucuronosyltransferases in endoplasmic reticulum membranes: advances and open questions. Biochem Pharmacol. 77(9), 1458-1465 (2009).
86. Radominska-Pandya A, Bratton S, Little JM. A historical overview of the heterologous expression of mammalian UDP-glucuronosyltransferase isoforms over the past twenty years. Curr. Drug Metab. 6(2), 141-160 (2005). (Pubitemid 40394342)
87. Coller JK, Christrup LL, Somogyi AA. Role of active metabolites in the use of opioids. Eur. J. Clin. Pharmacol. 65(2), 121-139 (2009).
88. Stachulski AV: The chemistry and biological activity of acyl glucuronides. Curr. Opin. Drug Discov. Devel. 10(1), 58-66 (2007). (Pubitemid 46438258)
89. Ritter JK. Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions. Chem. Biol. Interact. 129(1-2), 171-193 (2000). (Pubitemid 32061059)
90. Schulz C, Boeck S, Heinemann V, Stemmler HJ. UGT1A1 genotyping: a predictor of irinotecan-associated side effects and drug efficacy? Anticancer Drugs 20(10), 867-879 (2009).
91. Saudan C, Baume N, Robinson N, Avois L, Mangin P, Saugy M. Testosterone and doping control. Br. J. Sports. Med. 40 (Suppl. 1), i21-i24 (2006). (Pubitemid 44032626)
92. Alonen A, Gartman M, Aitio O, Finel M, Yli-Kauhaluoma J, Kostiainen R. Synthesis, structure characterization, and enzyme screening of clenbuterol glucuronides. Eur. J. Pharm. Sci. 37(5), 581-587 (2009).
93. Thevis M, Opfermann G, Schmickler H, Schanzer W. Mass spectrometry of steroid glucuronide conjugates. II-electron impact fragmentation of 3-keto-4-en- and 3-keto-5 a-steroid-17-o-ß glucuronides and 5 a-steroid-3 a,17ß-diol 3- and 17-glucuronides. J. Mass. Spectrom. 36(9), 998-1012 (2001). (Pubitemid 32938446)
94. Dell D. Labile metabolites. Chromatographia 59, S139-S148 (2004).
95. Johnson CH, Wilson ID, Harding JR et al. NMR spectroscopic studies on the in vitro acyl glucuronide migration kinetics of ibuprofen ((+/-)-(R,S)-2-(4- isobutylphenyl) propanoic acid), its metabolites, and analogues. Anal. Chem. 79(22), 8720-8727 (2007). (Pubitemid 350171385)
96. Kenny JR, Maggs JL, Meng X et al. Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac. J. Med. Chem. 47(11), 2816-2825 (2004). (Pubitemid 38656734)
97. Meng X, Maggs JL, Pryde DC et al. Cyclization of the acyl glucuronide metabolite of a neutral endopeptidase inhibitor to an electrophilic glutarimide: synthesis, reactivity, and mechanistic analysis. J. Med. Chem. 50(24), 6165-6176 (2007).
98. Al-Zoughool M, Talaska G. High performance liquid chromatography method for determination of N-glucuronidation of 4-aminobiphenyl by mouse, rat, and human liver microsomes. Anal. Biochem. 340(2), 352-358 (2005). (Pubitemid 40544875)
99. Luo H, Hawes EM, Mckay G, Midha KK. Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group. J. Pharm. Sci. 81(11), 1079-1083 (1992). (Pubitemid 23021429)
100. Mutlib AE, Nelson WL. Synthesis and identification of the N-glucuronides of norgallopamil and norverapamil, unusual metabolites of gallopamil and verapamil. J. Pharmacol. Exp. Ther. 252(2), 593-599 (1990). (Pubitemid 20101871)
101. Vashishtha SC, Hawes EM, Mckay G, McCann DJ. Synthesis and identification of the quaternary ammonium-linked glucuronide of 1-phenylimidazole in human liver microsomes and investigation of the human UDP-glucuronosyltransferases involved. Drug Metab. Dispos. 28(9), 1009-1013 (2000). (Pubitemid 30660352)
102. Pallmann T, Jonas U, Wagner M et al. Enzyme-assisted synthesis and structural characterization of pure benzodiazepine glucuronide epimers. Eur. J. Pharm. Sci. 29, 29 (2009).
103. Anderson S, Luffer-Atlas D, Knadler MP. Predicting circulating human metabolites: how good are we? Chem. Res. Toxicol. 22(2), 243-256 (2009).
104. Dragan CA, Buchheit D, Bischoff D, Ebner T, Bureik M. Glucuronide production by whole-cell biotransformation using genetically engineered fission yeast Schizosaccharomyces pombe. Drug Metab. Dispos. 38(3), 509-515 (2010).
105. Amadio J, Murphy CD. Biotransformation of fluorobiphenyl by Cunninghamella elegans. Appl. Microbiol. Biotechnol. 3, 3 (2009).
106. Collier AC, Keelan JA, Van Zijl PE, Paxton JW, Mitchell MD, Tingle MD. Human placental glucuronidation and transport of 3́azido-3́- deoxythymidine and uridine diphosphate glucuronic acid. Drug Metab. Dispos. 32(8), 813-820 (2004). (Pubitemid 38955610)
107. Freiser H, Jiang Q. Optimization of the enzymatic hydrolysis and analysis of plasma conjugated g-CEHC and sulfated long-chain carboxychromanols, metabolites of vitamin E. Anal. Biochem. 388(2), 260-265 (2009).
108. Liu X, Tam VH, Hu M. Disposition of flavonoids via enteric recycling: determination of the UDP-glucuronosyltransferase isoforms responsible for the metabolism of flavonoids in intact CACO-2 TC7 cells using SIRNA. Mol. Pharm. 4(6), 873-882 (2007).
109. Bai X, Xie YY, Liu J, Qu JL, Kano Y, Yuan D. Isolation and identification of urinary metabolites of kakkalide in rats. Drug Metab. Dispos. 38(2), 281-286 (2010).
110. Zhang ZF, Liu Y, Luo P, Zhang H. Separation and purification of two flavone glucuronides from Erigeron multiradiatus (lindl.) benth with macroporous resins. J. Biomed. Biotechnol. 11, 875629 (2009).
111. Kittelmann M, Rheinegger U, Espigat A et al. Preparative enzymatic synthesis of the acylglucuronide of mycophenolic acid. Biocatalysis 345(6-7), 825-829 (2003). (Pubitemid 37393169)
112. Caron P, Trottier J, Verreault M, Belanger J, Kaeding J, Barbier O. Enzymatic production of bile acid glucuronides used as analytical standards for liquid chromatography-mass spectrometry analyses. Mol. Pharm. 3(3), 293-302 (2006). (Pubitemid 44021435)
113. Schwaninger AE, Meyer MR, Zapp J, Maurer HH. The role of human UDP glucuronyltransferases on the formation of the methylenedioxymethamphetamine (ecstasy) phase II metabolites R- and S-3-methoxymethamphetamine 4-O-glucuronides. Drug Metab. Dispos. 37(11), 2212-2220 (2009).
114. Fujita K, Mogami A, Hayashi A, Kamataki T. Establishment of Salmonella strain expressing catalytically active human UDP-glucuronosyltransferase 1A1 (UGT1A1).LIFE Sci. 66(20), 1955-1967 (2000). (Pubitemid 30213169)
115. Dellinger RW, Chen G, Blevins-Primeau AS, Krzeminski J, Amin S, Lazarus P. Glucuronidation of phip and N-OH-phip by UDP-glucuronosyltransferase 1A10. Carcinogenesis 28(11), 2412-2418 (2007). (Pubitemid 350111602)
116. Fisher MB, Paine MF, Strelevitz TJ, Wrighton SA. The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metab. Rev. 33(3-4), 273-297 (2001). (Pubitemid 33136266)
117. Liu J, Balasubramanian MK. 1,3-β-glucan synthase: a useful target for antifungal drugs. Curr. Drug Targets Infect. Disord. 1(2), 159-169 (2001).
118. Tanaka N, Konomi M, Osumi M, Takegawa K. Characterization of Schizosaccharomyces pombe mutant deficient in UDP-galactose transport activity. Yeast 18(10), 903-914 (2001). (Pubitemid 32677314)
119. Passarinha LA, Bonifacio MJ, Queiroz JA. Application of a fed-batch bioprocess for the heterologous production of HSCOMT in Escherichia coli. J. Microbiol. Biotechnol. 19(9), 972-981 (2009).
120. Passarinha LA, Bonifacio MJ, Soares-Da-Silva P, Queiroz JA. A new approach on the purification of recombinant human soluble catechol-O- methyltransferase from an Escherichia coli extract using hydrophobic interaction chromatography. J. Chromatogr. A 1177(2), 287-296 (2008).
121. Wang H, Vath GM, Kawamura A et al. Over-expression, purification, and characterization of recombinant human arylamine N-acetyltransferase 1. Protein J. 24(2), 65-77 (2005). (Pubitemid 40875246)
122. Riches Z, Bloomer JC, Coughtrie MW. Comparison of 2-aminophenol and 4-nitrophenol as in vitro probe substrates for the major human hepatic sulfotransferase, SULT1A1, demonstrates improved selectivity with 2-aminophenol. Biochem. Pharmacol. 74(2), 352-358 (2007). (Pubitemid 46890815)
123. Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol. Sci. 25(4), 193-200 (2004). (Pubitemid 38519910)
124. Daly AK. Pharmacogenetics and pharmacogenomics. Pharmacogenomics 8(11), 1493-1496 (2007). (Pubitemid 350286394)
125. Rodriguez-Antona C, Jande M, Rane A, Ingelman-Sundberg M. Identification and phenotype characterization of two CYP3A haplotypes causing different enzymatic capacity in fetal livers. Clin. Pharmacol. Ther. 77(4), 259-270 (2005). (Pubitemid 40470382)
126. Dai D, Tang J, Rose R et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J. Pharmacol. Exp. Ther. 299(3), 825-831 (2001). (Pubitemid 33104948)
127. Blaisdell J, Jorge-Nebert LF, Coulter S et al. Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics 14(8), 527-537 (2004). (Pubitemid 39106854)
128. Kirchheiner J, Klein C, Meineke I et al. Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics. 13(10), 619-626 (2003). (Pubitemid 37311148)
129. Komori M, Nishio K, Ohi H, Kitada M, Kamataki T. Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome P450. J. Biochem. 105(2), 161-163 (1989). (Pubitemid 19059073)
130. Domanski TL, Finta C, Halpert JR, Zaphiropoulos PG. cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol. Pharmacol. 59(2), 386-392(2001). (Pubitemid 32108573)
131. Westlind A, Malmebo S, Johansson I et al. Cloning and tissue distribution of a novel human cytochrome P450 of the CYP3A subfamily, CYP3A43. Biochem. Biophys. Res. Commun. 281(5), 1349-1355 (2001). (Pubitemid 32924568)
132. Gellner K, Eiselt R, Hustert E et al. Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics. 11(2), 111-121 (2001). (Pubitemid 32216122)