Advances in microbial steroid biotransformation

Mahato, Shashi B.; Garai, Subhadra

doi:10.1016/s0039-128x(96)00251-6

Cited by 276 publications

(125 citation statements)

References 62 publications

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“…Portions of the combined residues (20 mg) were dissolved in MeOH (1.0 mL) for the injection into the apparatus. An ODS column (250 × 20 mm i.d., Shimadzu, Japan) was employed at room temperature, eluted with 84% aqueous CH 3 …”

Section: Biotransformation Experimentsmentioning

confidence: 99%

“…1 Biotransformation reactions can be accomplished at room temperature and in aqueous medium, presenting itself as a milder alternative to classical chemical reactions, [2][3][4] being employed for the resolution of racemates and to introduce chiral centers in substrates, among other uses. 5 Fungi are eukaryotic organisms that possess enzyme systems similar to those of mammalians.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Biotransformation of digitoxigenin by Cochliobolus lunatus

Pádua¹,

Oliveira²,

Filho³

et al. 2007

J. Braz. Chem. Soc.

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A reação de biotransformação da digitoxigenina (1) por Cochliobolus lunatus foi investigada. Foram realizados experimentos com duração de 4 dias, que resultaram no isolamento de quatro produtos, cujas estruturas químicas foram elucidadas como sendo 1β-hidroxidigitoxigenina (2), 7β-hidroxidigitoxigenina (3), 8β-hidroxidigitoxigenina (4) e digitoxigenona (5). A obtenção desses produtos nas condições empregadas nunca foi anteriormente descrita. A produção da substância 4 em uma reação de biotransformação também é inédita.The biotransformation of digitoxigenin (1) by Cochliobolus lunatus was investigated. The biotransformation reaction was carried out in a 4-day process, resulting in the isolation of four products, whose structures were elucidated as 1β-hydroxydigitoxigenin (2), 7β-hydroxydigitoxigenin (3), 8β-hydroxydigitoxigenin (4) and digitoxigenone (5). The production of these derivatives under the employed conditions has never been described so far. This is also the first report on the production of compound 4 by a biotransformation reaction.Keywords: digitoxigenin, Cochliobolus lunatus, 1β-hydroxydigitoxigenin, 7β-hydroxydigitoxigenin, 8β-hydroxydigitoxigenin, digitoxigenone IntroductionEnzymes are known to possess a wide substrate tolerance by keeping their exquisite catalytic properties with respect to chemo-, regio-and enantio-selectivity, playing an important role in biotransformations. 1 Biotransformation reactions can be accomplished at room temperature and in aqueous medium, presenting itself as a milder alternative to classical chemical reactions, 2-4 being employed for the resolution of racemates and to introduce chiral centers in substrates, among other uses. 5 Fungi are eukaryotic organisms that possess enzyme systems similar to those of mammalians. They usually present highly flexible metabolism, thus accepting varied sources of carbon and nitrogen. The ecological relations of these organisms include the metabolism of different secondary compounds, a feature sustained by diversified enzymatic systems, both intra and extra cellular, capable of carrying out numerous reactions. 6-8 Such attributes suggest fungi as suitable organisms to perform biotransformation reactions.The biotransformation of steroidal compounds by fungi has been extensively evaluated, including reactions with cardiac glycosides (Pádua et al. 9 and references herein; Table 3 of the present work). Digoxin, a Digitalis cardenolide, is still the drug of choice for the treatment of congestive heart failure, acting as a selective inhibitor of the Na + ,K + ATPase enzyme. Biotransformation of cardenolides has been investigated either as a strategy to obtain new derivatives or to convert the A-type cardenolides into the corresponding C-type compounds, which have clinical relevance. 9 The main reactions obtained so far for cardenolide biotransformation were hydroxylation in different positions of the steroidal skeleton, oxidation, glycosylation, epimerization and esterification of the hydroxyl group at C-3 (see Table 3 for references). An...

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Section: Biotransformation Experimentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biotransformation of digitoxigenin by Cochliobolus lunatus

Pádua¹,

Oliveira²,

Filho³

et al. 2007

J. Braz. Chem. Soc.

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“…Moreover, they did not study the actual influence of digestion of contaminated feed on cattle or, in this case, horses. [12] The conversion of phytosterols to steroids has been reported in other biological systems, [15] mainly involving a variety of microorganisms [16] such as Mycobacterium sp., [17][18][19] Arthrobacter, and Nocardia sp. [20] In addition, a number of studies have been devoted to the ability of invertebrate organisms to convert phytosterols into anabolic steroids: maggots of Lucilia Serica, [21] Crustaceae, [22] and zebra fish.…”

Section: Introductionmentioning

confidence: 99%

Mouldy feed: A possible explanation for the excretion of anabolic‐androgenic steroids in horses

Decloedt

Bailly-Chouriberry²,

Bussche

et al. 2016

Drug Testing and Analysis

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To ensure fair competition and to protect the horse's welfare, horses have to compete on their own merits, without any unfair advantage that might follow the use of drugs. Therefore, regulatory authorities list all substances that are not allowed in competition, including most anabolic-androgenic steroids. As zero-tolerance is retained, the question arose whether the consumption of mouldy feed could lead to the excretion of steroids, due to the biotransformation of plant phytosterols to steroids. A rapid ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analytical method, previously validated according to AORC (Association of Official Racing Chemists) and EC (European Commission) guidelines, was used to measure steroids in different sample types. Multiple mouldy feed samples were tested for the presence of steroids. The effect of digestion was tested by in vitro simulation of the horse's hindgut in batch incubations. In most feed samples no steroids were detected, even when the products were mouldy. Mouldy corn however showed to contain up to 3.0 ± 0.4 μg/kg AED (4-androstenedione), the main testosterone precursor. This concentration increased when mouldy corn (with added phytosterols) was digested in vitro. An herbal phytosupplement also showed to contain α-testosterone. These results demonstrate that it is important to caution against the consumption of any feed or (herbal) supplement of which the detailed ingredients and quantitative analysis are unknown. The consumption of mouldy corn should especially be avoided, not only from a horse health and welfare point of view, but also to avoid possible inadvertent positive doping results.

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“…The microbial biotransformation of steroids has attracted substantial interest in the pharmaceutical industry since the 1950s (Fernandes et al, 2003;Mahato & Garai, 1997). Through their biotransformation, a large variety of physiologically active steroid intermediates are produced (Horinouchi et al, 2003;Sedlaczek, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Through their biotransformation, a large variety of physiologically active steroid intermediates are produced (Horinouchi et al, 2003;Sedlaczek, 1988). These intermediates and their derivatives are utilized extensively as drugs and hormones because of their anti-inflammatory, diuretic, anabolic, contraceptive, anti-androgenic, progestational and anticancer properties (Donova, 2007;Mahato & Garai, 1997). The microbial steroid catabolic pathway has received even more attention since the discovery that this pathway is closely related to the pathogenicity of several pathogenic bacteria, e.g.…”

Section: Introductionmentioning

confidence: 99%

Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Δ¹-dehydrogenase fromRhodococcus erythropolisSQ1

Rohman

Oosterwijk

Dijkstra

2012

Acta Crystallogr F Struct Biol Cryst Commun

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3-Ketosteroid Á 1 -dehydrogenase plays a crucial role in the early steps of steroid degradation by introducing a double bond between the C1 and C2 atoms of the A-ring of its 3-ketosteroid substrates. The 3-ketosteroid Á 1 -dehydrogenase from Rhodococcus erythropolis SQ1, a 56 kDa flavoprotein, was crystallized using the sitting-drop vapour-diffusion method at room temperature. The crystals grew in various buffers over a wide pH range (from pH 5.5 to 10.5), but the best crystallization condition consisted of 2%(v/v) PEG 400, 0.1 M HEPES pH 7.5, 2.0 M ammonium sulfate. A native crystal diffracted X-rays to 2.0 Å resolution. It belonged to the primitive orthorhombic space group P2 1 2 1 2 1 , with unit-cell parameters a = 107.4, b = 131.6, c = 363.2 Å , and contained eight molecules in the asymmetric unit. The initial structure of the enzyme was solved using multiwavelength anomalous dispersion (MAD) data collected from a Pt-derivatized crystal.

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Advances in microbial steroid biotransformation

Cited by 276 publications

References 62 publications

Biotransformation of digitoxigenin by Cochliobolus lunatus

Biotransformation of digitoxigenin by Cochliobolus lunatus

Mouldy feed: A possible explanation for the excretion of anabolic‐androgenic steroids in horses

Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Δ¹-dehydrogenase fromRhodococcus erythropolisSQ1

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Advances in microbial steroid biotransformation

Cited by 276 publications

References 62 publications

Biotransformation of digitoxigenin by Cochliobolus lunatus

Biotransformation of digitoxigenin by Cochliobolus lunatus

Mouldy feed: A possible explanation for the excretion of anabolic‐androgenic steroids in horses

Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Δ1-dehydrogenase fromRhodococcus erythropolisSQ1

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Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Δ¹-dehydrogenase fromRhodococcus erythropolisSQ1