Abstract

The relationship between 17alpha-hydroxylation and 20-oxidation-reduction of progesterone and some of its derivatives was studied in yeast strains Saccharomyces cerevisiae YEp51alpha, Yarrowia lipolytica E129A15, and expressing cytochrome P450c17. The key metabolites were found to be 17alpha-hydroxyprogesterone and 17alpha,20(alpha,beta)-dihydroxypregn-4-ene-3-ones. The bioconversion pathways of pregn-4-ene-20(alpha,beta)-ol-3-ones were determined. They included cycles of 20-oxidation, 17alpha-hydroxylation, and stereospecific 20-reduction. The efficiency and kinetic parameters of steroid bioconversion by the recombinant strains were determined. The role of yeast analogs of mammalian steroid dehydrogenases is discussed. It was found that any of the desired derivatives, 17alpha-hydroxyprogesterone or progesterone 17alpha,20(alpha,beta)-diols, could be obtained from progesterone.

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