The Biotransformation of Some Steroids by Aspergillus Sydowii MRC 200653

Abstract

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.

Biotransformation of Androstenedione by Filamentous Fungi Isolated from Cultural Heritage Sites in the State Tretyakov Gallery

“…It turned out that all the studied strains were able to transform AD, with different efficiency and specificity ( Figure 3 ). Together with the current study, 23 possible steroid products have been described in the literature following the Aspergillaceae family steroid transformation of AD [ 16 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ] ( Table 2 , Figure 4 ). Of the steroid products found in our study, 21.7% (5 out of 23) had been previously described: TS ( e ), 6β–OH–AD ( l ), 6β–OH–TS, ( m ), 11β–OH–AD ( o ), and 14α–OH–AD ( p ).…”

Microbial Transformation of Epiandrosterone by Aspergillus Sydowii

“…In the previous work, A. sydowii dehydrogenated dehydroepiandrosterone predominantly and then hydroxylated it at C-6β, whilst the remaining dehydroepiandrosterone was hydroxylated only at C-7α or C-7β. 5 In this work, the 1α-hydroxylation of epiandrosterone 1 by A. sydowii could have been due to the hydration of the 1,2-double bond, as in the testosterone catabolism by Steroidobacter denitrificans. 25…”

“…4 There has been only one steroid biotransformation by A. sydowii reported in the literature. 5 In the present work, epiandrosterone 1 was incubated with A. sydowii MRC 200653 in order to investigate its metabolism by the fungus.…”

“…According to the literature, the dehydrogenation of steroids by some fungal species has been observed. 5,7,[15][16][17][18][19][20][21][22] Dehydrogenation in ring A of steroids is widely used in the production of corticosteroids. 23 Synthetic steroidal drugs with a 1,2-double bond have a greater affinity for the glucocorticoid receptors, and the presence of a 1,2-double bond together with a 3-keto-4ene moiety gives these compounds higher therapeutic potency by reducing their rate of metabolic degradation.…”

Latent Functions and Applications of Cytochrome P450 Monooxygenases from Thamnidium elegans: A Novel Biocatalyst for 14α-Hydroxylation of Testosterone

“…The functional identification of CYP5312A4 complements earlier notions that several fungi can convert testosterone to 14α-hydroxytestosterone even though metabolic systems involved in the reaction have not been identified. 22 , 25 , 26 Thus, functionomic studies may highlight latent potentials of fungal P450s hidden behind fungal biology.…”