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Research ArticleArticle

Heterologous Expression of Human Drug-metabolizing Enzymes

F. Peter Guengerich, Asit Parikh, Eric F. Johnson, Toby H. Richardson, Claes von Wachenfeldt, Jose Cosme, Frank Jung, Christian P. Strassburg, Michael P. Manns, Robert H. Tukey, Mike Pritchard, Sylvie Fournel-Gigleux and Brian Burchell
Drug Metabolism and Disposition November 1997, 25 (11) 1234-1241;
F. Peter Guengerich
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Asit Parikh
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Eric F. Johnson
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Toby H. Richardson
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Claes von Wachenfeldt
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Jose Cosme
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Frank Jung
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Christian P. Strassburg
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Michael P. Manns
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Robert H. Tukey
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Mike Pritchard
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Sylvie Fournel-Gigleux
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Brian Burchell
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Abstract

This article is a report on a symposium held at the March 1997 meeting of the American Society for Pharmacology and Experimental Therapeutics in San Diego. Current developments in the heterologous expression of cytochrome P450, NADPH-cytochrome P450 reductase, glutathione transferase, and UDP-glucuronosyltransferase enzymes are described. Systems include bacteria, insect cells, and transient and stable mammalian cells. Uses of the products are described for discernment of which enzymes are involved in metabolism of drugs, genotoxicity assays, mutagenesis (for structure-activity relationships), large scale production of enzyme products, antibody production, and production of proteins for biophysical studies.

Footnotes

  • Send reprint requests to: Prof. F. Peter Guengerich, Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146.

  • ↵4 M. Pritchard, unpublished results.

  • This work was supported in part by United States Public Health Service Grants CA44353, ES000267 (F.P.G.), GM07347 (A.P.), GM31001 (E.F.J.), GM 49135 (R.H.T.), and The Wellcome Trust and BBSRC (B.B.).

  • ↵3 P.I. Mackenzie, I.S. Owens, B. Burchell, K. W. Bock, A. Bairoch, A. Belanger, S. Fournelgigleux, M. Green, D. W. Hum, T. Lyanagi, D. Lancet, P. Louisot, J. Magdalou, J. R. Chowdhury, J. K. Ritter, H. Schachter, T. R. Tephly, K. F. Tipton, and D. W. Nebert: The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence.Pharmacogenetics 7, 255–269 (1997).

  • ↵2 P. M. Shaw, N. A. Hosea, D. V. Thompson, J. M. Lenius, and F. P. Guengerich: Reconstitution premixes for assays using recombinant human cytochrome P450, NADPH-cytochrome P450 reductase and cytochromeb5. Arch. Biochem. Biophy. (in press).

  • Abbreviations used are::
    P450
    cytochrome P450
    GSH
    glutathione
    UGT
    UDP-glucuronosyltransferase
    • Received May 27, 1997.
    • Accepted July 17, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition
Vol. 25, Issue 11
1 Nov 1997
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Research ArticleArticle

Heterologous Expression of Human Drug-metabolizing Enzymes

F. Peter Guengerich, Asit Parikh, Eric F. Johnson, Toby H. Richardson, Claes von Wachenfeldt, Jose Cosme, Frank Jung, Christian P. Strassburg, Michael P. Manns, Robert H. Tukey, Mike Pritchard, Sylvie Fournel-Gigleux and Brian Burchell
Drug Metabolism and Disposition November 1, 1997, 25 (11) 1234-1241;

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Research ArticleArticle

Heterologous Expression of Human Drug-metabolizing Enzymes

F. Peter Guengerich, Asit Parikh, Eric F. Johnson, Toby H. Richardson, Claes von Wachenfeldt, Jose Cosme, Frank Jung, Christian P. Strassburg, Michael P. Manns, Robert H. Tukey, Mike Pritchard, Sylvie Fournel-Gigleux and Brian Burchell
Drug Metabolism and Disposition November 1, 1997, 25 (11) 1234-1241;
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  • Article
    • Abstract
    • Expression of Mammalian Microsomal Cytochromes P450 and Their Redox Partner, NADPH-P450 Reductase, in Escherichia coli (E.F.J., T.H.R., C.v.W., J.C., F.J.)
    • Use of Bacterial Expressions Systems with Human P450s and GSH Transferases (F.P.G., A.P.)
    • Expression and Characterization of UGTs (C.P.S., M.P.M., R.H.T.)
    • Heterologous Expression of Human UDP-Glucuronosyltransferases in Mammalian Cells and E. coli (B.B., M.P., S.F-G.)
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