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Bioreactor Systems in Drug Metabolism: Synthesis of Cytochrome P450-Generated Metabolites by Thomas H. Rushmore; Paul J. Reider; Don Slaughter; Carol Assang; Magang Shou is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Bioreactor Systems in Drug Metabolism: Synthesis of Cytochrome P450-Generated Metabolites about?

In this communication, we report that suspension cultures of Sf 21 insect cells, co-infected with baculovirus containing the cDNA for a single cytochrome P450 and NADPH cytochrome P450 oxidoreductase, can be employed successfully as ``bioreactors'' for the synthesis of milligram quantities of cytochrome P450-generated metabolite(s). Three standard or probe substrates for the human P450s were chosen for the initial biosynthetic experiments: testosterone, diazepam, and diclofenac. Testosterone (100 + M, 2.88 mg100 ml), added to a 100-ml CYP3A4 bioreactor, was converted to 6;-hydroxytestosterone (2.3 mg) and 15;-hydroxytestosterone (0.18 mg). Diazepam (100 + M, 2.9 mg 100 ml), added to a 100-ml CYP3A4 bioreactor, was converted to temazepam (1.1 mg), N-demethyldiazepam (0.35 mg), and oxazepam (0.15 mg). Diclofenac (100 + M, 3.18 mg 100 ml), added to a 100-ml CYP2C9 bioreactor, was converted to 4$-hydroxydiclofenac (2.6 mg). Since the goal for the development of the bioreactors was to provide a platform for both the production and subsequent purification of milligram quantities of P450-generated metabolite(s), a second 100-ml CYP2C9 bioreactor was used for the large-scale production

Who reads Bioreactor Systems in Drug Metabolism: Synthesis of Cytochrome P450-Generated Metabolites?

Author

Thomas H. Rushmore; Paul J. Reider; Don Slaughter; Carol Assang; Magang Shou

Publisher

Elsevier Science; Elsevier ; Elsevier Inc.; Elsevier BV (ISSN 1096-7176)

Published

2000

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)