[Effect of steroid biosynthesis modificators on the progesterone biotransformation by a recombinant yeasts expressing cytochrome P450c17].
Using the recombinant microorganisms S. cerevisiae GRF18 YEp5117alpha, expressing cytochrome P450c17 from bovine adrenal cortex, we investigated the influence of the various modificators of steroids biosynthesis on the relationship between the 17alpha-hydroxylation of progesterone and 20alpha-reduction. Dexamethasone and metirapon had no effect on the reaction of progesterone 17alpha-hydroxylation and on the reaction of 17alpha-hydroxyprogesterone 20alpha-reduction. Mifepriston and danazol did not covalently modify amino acid residues of the cytochrome P450c17 or its heme group under the conditions of the biotransformation of progesterone by recombinant yeasts. Ketokonazol, mifepriston and danazol acted as low-affinity competitive inhibitors, but the 20-dihydro derivatives of progesterone were mixed type inhibitors for the cytochrome P450c17. All modifiers that we used did not influence the functional properties of the yeast analog of 20alpha-hydroxysteroid dehydrogenase. According to the influence on the catalytic parameters of the cytochrome P450c17, the modifiers used can be arranged in the following order: 20beta-dihydroprogesterone (maximum effect) > mifepriston = ketokonazol > 20alpha-dihydroprogesteron > danazol > dexamethasone, metirapon (without effect).
Shkumatov
V M
VM
Usova
E V
EV
Frolova
N S
NS
Barth
G
G
Mauersberger
S
S
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology; D043607:20-alpha-Hydroxysteroid Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000302:Adrenal Cortex / Q000201:enzymology; D000818:Animals; D002417:Cattle; D003613:Danazol / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008797:Metyrapone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; D004092:20-alpha-Dihydroprogesterone; D015735:Mifepristone; D011374:Progesterone; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D013254:Steroid 17-alpha-Hydroxylase; D003613:Danazol; D007654:Ketoconazole; D008797:Metyrapone