Progesterone metabolism by the filamentous fungus Cochliobolus lunatus

Vitas, Marko; Smith, Kelvin E.; Rozman, Damjana; Komel, Radovan

doi:10.1016/0960-0760(94)90305-0

Cited by 37 publications

(19 citation statements)

References 13 publications

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“…The incubation was carried out at 28 C and 130 rpm for 2 h and terminated by addition of 3 ml of chloroform. Reaction mixtures were extracted and separated as described previously (Vitas et al, 1994(Vitas et al, , 1997. The cell fractionation method was investigated with localization studies of subcellular marker enzymes.…”

Section: Cell Breakage and In Vitro Studiesmentioning

confidence: 99%

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Biotransformation of steroids by the fission yeastSchizosaccharomyces pombe

Pajič

Vitas

Žigon

et al. 1999

Yeast

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The fungal biotransformation of steroids is of applied interest due to the economic importance of such stereo‐ and regiospecific reactions and also in the context of ergosterol pathway engineering to produce vitamin D and steroidal products. In Schizosaccharomyces pombe no steroid hydroxylation as is found in filamentous fungi was observed, but a cytosolic NAD(H)/NADP(H)‐dependent hydroxysteroid dehydrogenase activity was identified. Progesterone was reduced at the Δ4 double bond (in vivo only) as well as at the C‐3 and C‐20 keto groups. Testosterone and 4‐androstene‐3,17‐dione were interconverted and 5α‐pregnane‐3,20‐dione and 5β‐pregnane‐3,20‐dione were reduced to 3‐hydroxy products. The reactions were sometimes reversible and showed regio‐ and stereo specificity. In S. pombe more than one steroid dehydrogenase homologue is likely to occur, as has been observed in Saccharomyces cerevisiae. Our findings indicate that genes encoding soluble proteins should be examined as candidates for actual steroid dehydrogenase activity. Copyright © 1999 John Wiley & Sons, Ltd.

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Section: Cell Breakage and In Vitro Studiesmentioning

confidence: 99%

“…The reaction was terminated by adding chloroform to the cells and medium that were extracted separately. Extraction, separation and isolation of the biotransformation products were performed as described elsewhere (Vitas et al, 1994(Vitas et al, , 1997Lisboa, 1969).…”

Section: In Vivo Bioconversion Of Steroidsmentioning

confidence: 99%

Biotransformation of steroids by the fission yeastSchizosaccharomyces pombe

Pajič

Vitas

Žigon

et al. 1999

Yeast

Self Cite

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“…cubense responsible for Panama disease on banana, was shown previously to hydroxylate progesterone by introducing a hydroxyl group at position 15␣ [14]. We found that progesterone hydroxylase in F. oxysporum is induced by the presence of the steroidal substrate, as in other fungi [3,4], and proceeded to investigate the underlying mechanism of signal transduction by the mean of target knockout strains. The present work aims to give insight into the possible pathways leading to cytochrome P450-mediated steroid detoxification observed in several filamentous fungal species.…”

Section: Introductionmentioning

confidence: 99%

“…This biotransformation is economically relevant, because certain steroid metabolites are pharmacologically active and can be used in the synthesis of other steroids [2]. Specifically, the filamentous fungi Rhizopus nigricans and Cochliobolus lunatus were shown to convert the steroid progesterone into the pharmaceutically important compound 11␣-hydroxyprogesterone [3,4]. Although the biological role of progesterone transformation in fungi is currently unknown, it has been suggested as a mechanism for enzymatic detoxification of a fungitoxic substrate [5].…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Poli¹,

Pietro²,

Žigon³

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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a b s t r a c tFungi present the ability to hydroxylate steroids. In some filamentous fungi, progesterone induces an enzyme system which converts the compound into a less toxic hydroxylated product. We investigated the progesterone response in the vascular wilt pathogen Fusarium oxysporum, using mass spectrometry and high performance liquid chromatography (HPLC). Progesterone was mainly transformed into 15␣-hydroxyprogesterone, which was found predominantly in the extracellular medium. The role of two conserved fungal signaling cascades in the induction of the progesterone-transforming enzyme system was studied, using knockout mutants lacking the mitogen-activated protein kinase Fmk1 or the heterotrimeric G-protein ␤ subunit Fgb1 functioning upstream of the cyclic adenosine monophosphate (cAMP) pathway. No steroid hydroxylation was induced in the fgb1 strain, suggesting a role for the G-protein ␤ subunit in progesterone signaling. Exogenous cAMP restored the induction of progesteronetransforming activity in the fgb1 strain, suggesting that steroid signaling in F. oxysporum is mediated by the cAMP-PKA pathway.

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“…6,11 The fungus Cochliobolus lunatus and its conidial anamorphous form Curvularia lanata are known for their capacity of hydroxylating Δ 4-5 steroids. 12 The substrate induced 11β-hydroxylation of steroids is a classical biotransformation reaction carried out by this fungus, which tolerates structure variation in substrates. Apart from 11β position ("normal binding"), the major sites for C. lunatus hydroxylation are 14α and 7α resulting from inverted and reverse inverted binding of enzyme to steroid, respectively.…”

Section: Introductionmentioning

confidence: 99%

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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Progesterone metabolism by the filamentous fungus Cochliobolus lunatus

Cited by 37 publications

References 13 publications

Biotransformation of steroids by the fission yeastSchizosaccharomyces pombe

Biotransformation of steroids by the fission yeastSchizosaccharomyces pombe

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Biotransformation of digitoxigenin by Cochliobolus lunatus

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