Whole-cell biotransformation assay for investigation of the human drug metabolizing enzyme CYP3A7

Biochimica Et Biophysica Acta
Ina NeunzigMatthias Bureik

Abstract

The cytochrome P450 isoform CYP3A7 (wildtype) is the major form of CYP in human fetal liver. Since it is not exclusively expressed in the fetus but also in a significant number of adults, CYP3A7 has been moving into the focus of investigation on adverse drug reactions and interindividual differences in drug metabolism in the last few years. In addition, CYP3A7 is overexpressed in hepatocellular carcinoma (HCC), where it contributes to the elimination of drugs. We here report the development of a convenient and reliable whole-cell system for testing CYP3A7 activity using recombinant fission yeast. As expected, catalytic properties of wild type CYP3A7.1 and its polymorphic form CYP3A7.2 towards DHEA and testosterone resembled those reported previously. Interestingly, both isoforms of CYP3A7 did not metabolize the anti-cancer drug sorafenib (which is approved for the treatment of HCC), while CYP3A4 produced the N-oxide in our system, as expected. This finding suggests that CYP3A7 activity does not influence the effectiveness of this anti-cancer drug against HCC. Furthermore, CYP3A7-expressing fission yeast cells specifically converted a luciferin-derivate (luciferin-PFBE) to a luminescent product and this activity can conveniently...Continue Reading

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Citations

Aug 18, 2012·Applied Biochemistry and Biotechnology·Ina NeunzigMatthias Bureik
Jun 6, 2013·Applied Biochemistry and Biotechnology·Ina NeunzigMatthias Bureik
Jan 10, 2012·Journal of Biotechnology·Ina NeunzigMatthias Bureik
Apr 10, 2013·Progress in Lipid Research·Tamara Wriessnegger, Harald Pichler
Aug 23, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Odette A FahmiJerome M Lasker
Dec 2, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kojiro KawadaShinsaku Ito
Feb 17, 2021·Archives of Biochemistry and Biophysics·Dawit M WeldemichaelMatthias Bureik
Apr 19, 2021·Drug Metabolism and Pharmacokinetics·Yasushi Yamazoe, Masahiro Tohkin

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