Jadwiga Dmochowska-Gładysz

Steroids' transformations in Penicillium notatum culture.

The application of Penicillium notatum genus for biotransformations of steroids has been investigated. The reactions observed include insertion of an oxygen atom into D-ring of steroids, 15alpha-hydroxylation of 17alpha-methyl testosterone derivatives, ester bond hydrolysis, and degradation of a testosterone derivatives side chain. Microbial production of testolactones, the biologically active compounds, was also achieved using this strain in up to 98% yield.

Biotransformation XXXIX. Metabolism of testosterone, androstenedione, progesterone and testosterone derivatives in Absidia coerulea culture.

The strain of Absidia coerulea was used to investigate the transformations of testosterone, androstenedione, progesterone and testosterone derivatives with additional Cl-C2 double bond and/or 17alpha-methyl group. All the examined substrates were transformed, mainly hydroxylated. It was found that the position and stereochemistry of the introduced hydroxyl group, as well as the yield of products, depended on the structure of the substrate. The first three substrates (hormones) underwent hydroxylation at C-14, and additional hydroxylation at 7alpha was observed in progesterone. The presence of the double bond (C1-C2) in 1-dehydrotestosterone did not influence the position of hydroxylation, but the product with additional C14-C15 double bond (at the same site as hydroxylation) was formed. 17alpha-Methyltestosterone was hydroxylated at the 7alpha position, and also the dehydrogenated product (at the same site, with C6-C7 double bond) was obtained. The testosterone derivative with both C1-C2 double bond and 17alpha-methyl group underwent hydroxylation at the 7alpha or 11beta position, and a little amount of 14alpha, 15alpha epoxide was formed.

Transformations of steroids by Beauveria bassiana.

The course of transformations of testosterone and its derivatives, including compounds with an additional C1,C2 double bond and/or a 17α-methyl group, a 17β-acetyl group or without a 19-methyl group, by a Beauveria bassiana culture was investigated. The fungi promoted hydroxylation of these compounds at position 11α, oxidation of the 17β-hydroxyl group, reduction of the C1,C2 or C4,C5 double bonds and degradation of the progesterone side-chain, leading to testosterone. The structure of 4-ene-3-oxo-steroids had no influence on regio- and stereochemistry of hydroxylation. In a similar manner, dehydroepiandrosterone was hydroxylated by Beauveria bassiana at position 11α, however, a small amount of 7α- hydroxylation product was also formed.

Microbial transformation of selected flavanones as a method of increasing the antioxidant properties.

Antioxidant properties of substrates [fl avanone (1), 6-hydroxy- (2), 7-hydroxy- (3), 5,7,4’- trihydroxy- (5), and 7-methoxyfl avanone (4)] and products of their microbial transformations, comprising hydroxylation, O-methylation, stereospecifi c reduction, dehydrogenation, and C-ring cleavage of the benzo-γ-pyrone system, were determined. Measurements of the antiradical activity (expressed as IC50 value) of both the substrates and the products led to the determination of the impact of type and location of substituents in the tested fl avonoids on changes in their antioxidant activities.

Microbial transformations of 6- and 7-methoxyflavones in Aspergillus niger and Penicillium chermesinum cultures.

A detailed study of the biotransformation of 6- and 7-methoxyfl avones by four fungal strains (Aspergillus niger strains MB, KB, and SBP; Penicillium chermesinum 113) was carried out. Products of demethylation and also demethylation combined with hydroxylation at C-4’ were identifi ed. The biotransformation products were stronger antioxidants than the substrates.

Biotransformation—XXXIV. Metabolism of testosterone esters in fungi cultures

Seven esters of testosterone: acetate, propionate, enanthate, caprate, undecanoate, isobutyrate and isocaproate (some of them are used as drugs) were transformed by microorganisms: Absidia coerulea, Acremonium roseum, Aphanocladium album and Rhodotorula mucilaginosa to obtain some information about their metabolism. It was observed that the presence and structure of the acyl group mainly influenced the degree of transformation. The first step of the reaction was probably hydrolysis of ester, followed by testosterone transformation. Only the branched chain esters were transformed by R. mucilaginosa without hydrolysis of the ester bond.