Biotransformations of epiandrosterone (1), dehydroepiandrosterone (2), testosterone (3), progesterone (4) and pregnenolone (5) by Aspergillus tamarii MRC 72400 for 5 days have been reported and the results of these incubations have been compared with previously published data obtained with Aspergillus tamarii QM 1223. A. tamarii MRC 72400 showed higher Bayer-Villiger monooxygenase activities than A. tamarii QM 1223 did. Apart from pregnenolone (5), A. tamarii MRC 72400 metabolized these steroids in different ways. Incubation of epiandrosterone (1) afforded 3β,11β-dihydroxy-5α-androstan-17-one (6) (3%) and 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one (7) (9.5%). Incubation of dehydroepiandrosterone (2) afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (28%), testolactone (9) (6%), 3β,7β-dihydroxyandrost-5-en-17-one (10) (13%) and 3β,7α-dihydroxyandrost-5-en-17-one (11) (24%). Incubation of testosterone (3) afforded testolactone (9) (58%). Incubation of progesterone (4) also afforded testolactone (9), however in higher yield (86%). Incubation of pregnenolone (5) afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one (8) (25%) and testolactone (9) (27%).A number of investigations involving microbial biotransformations of a wide range of steroidal substrates have been carried out due to their potential for the preparation of more valuable and functionalized compounds such as steroid drugs and hormones 1-3 . There are still enormous efforts to increase the efficiency of microbial steroid biotransformations and to find new useful microorganisms and reactions 1 . For example, some of these steroid biotransformations have been carried out using Aspergillus wentii 4 , Penicillium digitatum 5 and Aspergillus terreus 6 . A. wentii showed some high hydroxylase activities whereas P. digitatum and A. terreus showed some low 5α-reductase and Baeyer-Villiger monooxygenase (BVMO) activities, respectively.
First steroid biotransformations performed by Aspergillus wentii MRC 200316 are reported. Testosterone (1) yields 6β-hydroxytestosterone (3) and 14α-hydroxytestosterone (4) while progesterone (2) yields 11α-hydroxyprogesterone (5).
pathogen for humans. 4 Steroid biotransformations by A. candidus have not been described in the literature. In this work, dehydroepiandrosterone 1, progesterone 2 and pregnenolone 3 were incubated with A. candidus MRC 200634 for 5 days.Incubation of dehydroepiandrosterone 1 with A. candidus MRC 200634 for 5 days afforded six metabolites (Table 1). The first metabolite was identified as 3β,17β-dihydroxyandrost-5-ene 4 (Fig. 1). The metabolite had a new resonance (1H, t, J = 8.5 Hz) at δ H 3.65 ppm in its 1 H NMR spectrum and showed an upfield shift (Δ 0.11 ppm) for the 18-methyl resonance of the starting material, suggesting the presence of a 17β-hydroxy group. The 13 C NMR spectrum of the metabolite lacked the C-17 resonance of 1 at δ C 221.30 ppm and had a new carbon atom resonance at δ C 81.87 ppm (Table 2), which were in accordance with the reduction at C-17.The second metabolite was identified as 6β,17βdihydroxyandrost-4-en-3-one 5. The metabolite showed characteristic resonances at δ H 4.34 ppm 5 (1H, bs) and δ C 72.56 ppm 6 , suggesting the presence of a 6β-hydroxy group. The 1 H NMR spectrum of the metabolite lacked the 3-H resonance of starting material at δ H 3.46 ppm (1H, tt, J = 5.0 and 12.0 Hz) and the double bond resonance of 1 at δ H 5.35 ppm (1H, d, J = 5.0 Hz) had an important downfield shift to δ H 5.82 ppm (∆ 0.47 ppm), suggesting that the 5-en-3β-hydroxy moiety of 1 was converted into the 4-en-3-keto moiety. The 1 H NMR spectrum of the metabolite demonstrated a significant downfield shift (∆ 0.37 ppm) for the 19-methyl group, further suggesting the presence of the 4-en-3-keto moiety. The metabolite had a new resonance (1H, t, J = 8.5 Hz) at δ H 3.65 ppm in its 1 H NMR spectrum and showed an upfield shift (Δ 0.05 ppm) for the
The biotransformations of testosterone, epiandrosterone, progesterone and pregnenolone byAspergillus terreusMRC 200365 for five days were described. The biotransformation of testosterone afforded testolactone. The biotransformation of epiandrosterone afforded 3β-hydroxy-17a-oxa-D-homo-5α-androstan-17-one. The biotransformation of progesterone afforded androst-4-ene-3,17-dione and testolactone. The biotransformation of pregnenolone afforded 3β-hydroxy-17a-oxa-D-homoandrost-5-en-17-one and testolactone.
Fungal steroid biotransformations have been widely used for a long time in order to convert and synthesize steroids due to their remarkable regio-and stereo-selectivities. 1 Aspergillus species have been extensively studied in the context of mycotoxin production, pathogenicity, fundamental eukaryotic genetics and in biotechnology. 2 They are ubiquitous fungi found in soil, water and decaying materials. A few Aspergillus species are considered pathogenic to humans and animals. 3 The fungus Aspergillus sydowii is a mesophilic soil and marine saprophyte and it is a food contaminant and an opportunistic pathogen for humans. 4 Biotransformations of steroids by A. sydowii have not been described in the literature. In this work, testosterone 1, dehydroepiandrosterone 2, progesterone 3 and pregnenolone 4 were incubated with A. sydowii MRC 200653 for 5 days.Incubation of testosterone 1 with A. sydowii MRC 200653 for 5 days yielded three metabolites (Table 1). The first metabolite was identified as 6β,17β-dihydroxyandrost-4-en-3-one 5 (Fig. 1). The metabolite had new resonances at δ H 4.35 ppm (1H, bs) 5 and δ C 72.57 ppm 6 (Table 2), which were characteristic of a 6β-hydroxy group. The 1 H NMR spectrum of the metabolite showed a downfield shift (∆ 0.10 ppm) for the 4-H resonance of 1 at δ H 5.71 ppm (1H, s), supporting the presence of a 6β-hydroxy group. The 13 C NMR spectrum of the metabolite showed a downfield shift for C-7 (∆ 5.77 ppm), whereas it showed a γ-gauche upfield shift for C-8 (∆ 5.53 ppm), further supporting the presence of a 6β-hydroxy group.The second metabolite was identified as 14α,17βdihydroxyandrost-4-en-3-one 6. The 13 C NMR spectrum of the metabolite had a new carbon resonance at δ C 83.30 ppm, showing the presence of a hydroxy group. There was a significant downfield shift (∆ 0.70 ppm) for the 17α-H resonance suggesting a diaxial interaction with a 14α-hydroxy group. The 13 C NMR spectrum of the metabolite showed downfield shifts for C-8 (∆ 3.66 ppm) and C-15 (∆ 3.15 ppm) and there were γ-gauche upfield shifts for C-9 (∆ 6.78 ppm) and C-16 (∆ 0.12 ppm). These shifts revealed that a 14α-hydroxylation had taken place.
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