Bioconversion of 6-(N-methyl-N-phenyl)aminomethyl androstane steroids by Nocardioides simplex.

The newly synthesized (α/ß)-diastereomers of 6-(N-methyl-N-phenyl)aminomethylandrost-4-ene-3,17-dione (5) and 6-(N-methyl-N-phenyl)aminomethylandrost-4-en-17ß-ol-3-one (6) were firstly investigated as substrates for the whole cells of Nocardioides simplex VKM Ac-2033D in comparison with their unsubstituted analogs, - androst-4-ene-3,17-dione (1) and androst-4-en-17ß-ol-3-one (2). 1(2)-Dehydroderivatives were identified as the major bioconversion products from all the substrates tested. When using the mixtures of (α/ß)-stereoisomers of 5 and 6 as the substrates, only ß-stereoisomers of the corresponding 1,4-diene-steroids were formed. Along with 1(2)-dehydrogenation, N. simplex VKM Ac-2033D promoted oxidation of the hydroxyl group at C-17 position of 6: both 6(α) and 6(ß) were transformed to the corresponding 17-keto derivatives. No steroid core destruction was observed during the conversion of the 6-substituted androstanes 5 and 6, while it was significant when 1 or 2 was used as the substrate. The results suggested high potentials of N. simplex VKM Ac-2033D for the generation of novel 1(2)-dehydroanalogs.

Hydroxylation of carbazoles by Aspergillus flavus VKM F-1024.

Carbazole was metabolized by Aspergillus flavus VKM F-1024 forming few monohydroxylated products. The structure of metabolites was determined by TLC, GC, MS and (1)H NMR analyses. 3-Hydroxycarbazole was revealed as a major bioconversion product, 1-hydroxy- and 2-hydroxycarbazoles were observed as minor products. In the presence of 1-benzoylindole, the hydroxylation position shifted toward preferable accumulation of 2-hydroxycarbazole and the formation of 2,6- and 2,7-dihydroxycarbazoles. This effect and microbial formation of these metabolites have never been reported before. At the conversion of N-acetyl- and N-benzoylcarbazoles, carbazole was the major product, while 1-, 2- and 3-monohydroxycarbazoles were formed in small amounts.

Microbial conversion of pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione acetates by Nocardioides simplex VKM Ac-2033D.

The conversion of pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione 21-acetate (I) and 17,21-diacetate (VI) by Nocardioides simplex VKM Ac-2033D was studied. The major metabolites formed from I were identified as pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 21-acetate (II) and pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione (IV). Pregna-4,9(11)-diene-17alpha,21-diol-3,20-dione (III) and pregna-1,4,9(11)-triene-17alpha,20beta,21-triol-3-one (V) were formed in minorities. Biotransformation products formed from VI were pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 17,21-diacetate (VII), pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 21-acetate (II), pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione (IV), pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 17-acetate (VIII), pregna-1,4,9(11)-triene-17alpha,20beta,21-triol-3-one (V). The conversion pathways were proposed including 1(2)-dehydrogenation, deacetylation, 20beta-reduction and non-enzymatic migration of acyl group from position 17 to 21. The conditions providing predominant accumulation of pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 21-acetate (II) from I and pregna-1,4,9(11)-triene-17alpha,21-diol-3,20-dione 17-acetate (VIII) from VI in a short-term biotransformation were determined.