| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 69847 | Journal of Molecular Catalysis B: Enzymatic | 2012 | 8 Pages |
Dehydroepiandrosterone (DHEA) (10) and its five derivatives: testosterone (1), androstenedione (2), 17α-methyltestosterone (6), progesterone (13) and pregnenolone (14) were subjected to microbial transformation by the filamentous fungus Didymosphaeria igniaria KCH 6670. The predominant metabolism of the incubated 5-ene steroids (10 and 14) occurred through 3β-hydroxy-steroid dehydrogenase/5,4-en isomerase pathways resulting in the generation of a 4-en-3-oxo system on ring-A. The transformations of C19 steroids (1, 2, and 10) included a hydroxylation at 7α position, ketone–alcohol interconversion at C-17 and reduction of the double bond at C-4 and 3-keto group to the 3β-alcohol with 5α-stereochemistry at A/B ring. D. igniaria also carried out 6(7)-dehydrogenation and 6,7β-epoxidation during transformation of DHEA. Under these conditions transformation of DHEA (10) gave four products: 7α-hydroxyandrost-4-en-3,17-dione (4), 17β-hydroxyandrost-4,6-dien-3-one (11), 17β-hydroxyandrost-6β-epoxy-4-en-3-one (12) and 3β,17β-dihydroxy-5α-androstane (5). The compounds 11 and 12 are identified as DHEA metabolites for the first time. The transformation of C21 steroids (13 and 14) led to the mixture of mono- (mainly 11α- and 15β-) and dihydroxy- (7α,15β-; 14α,15β-; 11α,15β-; 11α,14α-) products. 7α,15β-Dihydroxypregnan-4-en-3,20-dione (18) and 14α,15β-dihydroxypregnan-4-en-3,20-dione (19) were found to be new compounds. The main product of transformation of 17α-methyltestosterone (6) was 12β-hydroxy-17α-methyltestosterone (7). The results of these transformations demonstrate the dependence of hydroxylation position on the structure of steroid nucleus.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► This is the report where D. igniaria successfully hydroxylated steroids. ► The primary route of 5-ene steroid metabolism generating of 3-one-4-ene system. ► The relationship between the substrates and hydroxylated position was discussed. ► Two new metabolites of DHEA and two new derivative of progesterone were obtained.
