Fungal transformation of methyltestosterone by the soil ascomycete Acremonium strictum to some hydroxy derivatives of 17-methylsteroid

Nassiri-Koopaei, Nasser; Mogharabi, Mehdi; Amini, Mohsen; Shafiee, Abbas; Faramarzi, Mohammad Ali

doi:10.1007/s10600-013-0703-0

Cited by 10 publications

(5 citation statements)

References 23 publications

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“…Product structures were determined by proton nuclear magnetic resonance ( 1 H-NMR), carbon-13 nuclear magnetic resonance ( 13 C-NMR) ( Table 1 ), heteronuclear multiple-bond correlation spectroscopy (HMBC), heteronuclear multiple-quantum correlation spectroscopy (HMQC), gas chromatography (GC) and thin-layer chromatography (TLC). The spectral characteristics of obtained compounds were in agreement with literature data [ 4 , 28 , 68 , 69 , 70 ].…”

Section: Resultssupporting

confidence: 88%

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Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations

et al. 2017

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The catalytic activity of enzymes produced by an entomopathogenic filamentous fungus (Isaria fumosorosea KCh J2) towards selected steroid compounds (androstenedione, adrenosterone, progesterone, 17α-methyltestosterone and dehydroepiandrosterone) was investigated. All tested substrates were efficiently transformed. The structure of the substrate has a crucial impact on regio- and stereoselectivity of hydroxylation since it affects binding to the active site of the enzyme. Androstenedione was hydroxylated in the 7α-position to give a key intermediate in the synthesis of the diuretic-7α-hydroxyandrost-4-ene-3,17-dione with 82% conversion. Adrenosterone and 17α-methyltestosterone were hydroxylated in the 6β-position. Hydroxylated derivatives such as 15β-hydroxy-17α-methyltestosterone and 6β,12β-dihydroxy-17α-methyltestosterone were also observed. In the culture of Isaria fumosorosea KCh J2, DHEA was effectively hydroxylated in the C-7 position and then oxidized to give 7-oxo-DHEA, 3β,7α- and 3β,7β-dihydroxy-17a-oxa-d-homo-androst-5-ene-17-one. We obtained 7β-OH-DHEA lactone with 82% yield during 3 days transformation of highly concentrated (5 g/L) DHEA.

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Section: Resultssupporting

confidence: 88%

“…Additionally, 6β-OH-17mT was hydroxylated in the 12β position, giving the dihydroxylated derivative 6β,12β-OH-17mT ( Scheme 3 ). 6β-Hydroxy- and dihydroxy derivatives were obtained in the culture of Acremonium strictum [ 70 ].…”

Section: Resultsmentioning

confidence: 99%

Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations

et al. 2017

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“…[38] 1-dehydro-17α-methyltestosterone (30, C 20 The corresponding 13 C shift at 72.4 ppm (rather than ca. 68 ppm) [155] indicated 6β-hydroxy-17α-methyltestosterone to be the product, which was confirmed by literature data on the same compound [156,157] or its (unmethylated) testosterone equivalent. [38,151] 15β-hydroxy-17α-methyltestosterone ( H).…”

Section: (+)-(4r5s7r11s)-supporting

confidence: 76%

Natural Product Diversification by One‐Step Biocatalysis using Human P450 3A4

et al. 2021

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Efficient synthetic techniques for the diversification of natural products are incremental for drug discovery processes of the pharmaceutical industry because these complex bioactive compounds often require an adjustment of properties. Human liver P450 3A4, key player of the body's detoxification system and decisive factor of a drug's metabolic fate, is renowned for its broad substrate scope including many natural products. In this study, we investigated the synthetic potential of human P450 3A4 for the diversification of natural product classes and isolated the produced metabolites of six selected natural products at a preparative 100-mg scale. Aided by efficient expression levels in P. pastoris, this whole-cell biocatalyst was found to be highly effective at the intended job allowing the identification of a total of 31 authentic human metabolites, many of them for the first time. By revealing an unprecedented degree of diversification, this study extends the synthetic repertoire for efficient enzymatic natural product modification in a one-step fashion and adds a completely new view to an old enzyme traditionally used for inhibition and toxicology studies.

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“…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.…”

mentioning

confidence: 99%

“…7,23 Introduction of a 1,2-double bond into the steroids is very rare in fungi although it is very common in bacteria. 24 Only a few fungi, such as Phycomyces blakesleeanus, 15 Nectria haematococca, 16 Trichoderma hamatum, 17 Cephalosporium aphidicola, 18 Fusarium lini, 7,18 Fusarium oxysporum, 19 Acremonium strictum 20 and Aspergillus niger, 21 were known to perform this type of dehydrogenation. In this work, A. sydowii carried out the introduction of both a 1,2-double bond and a 4,5-double bond into the substrate simultaneously as well as separately.…”

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confidence: 99%

Microbial Transformation of Epiandrosterone by Aspergillus Sydowii

Yildirim

Kuru

2016

Journal of Chemical Research

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Incubation of epiandrosterone with Aspergillus sydowii MRC 200653 afforded ten metabolites. The fungal dehydrogenation of epiandrosterone is reported for the first time. The formation of the major metabolite, 6β-hydroxyandrost-4-ene-3,17-dione, involved first dehydrogenation to give a 4-ene and then hydroxylation at C-6β. Small amounts of the substrate were hydroxylated at C-1α, C-7α, C-7β and C-11α.

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Fungal transformation of methyltestosterone by the soil ascomycete Acremonium strictum to some hydroxy derivatives of 17-methylsteroid

Cited by 10 publications

References 23 publications

Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations

Isaria fumosorosea KCh J2 Entomopathogenic Strain as an Effective Biocatalyst for Steroid Compound Transformations

Natural Product Diversification by One‐Step Biocatalysis using Human P450 3A4

Microbial Transformation of Epiandrosterone by Aspergillus Sydowii

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