INTERMEDIATES IN THE METABOLISM OF STEROIDS BY
            <i>PENICILLIUM LILACINUM</i>

Sebek, Oldrich K.; Reineke, L. M.; Peterson, D. H.

doi:10.1128/jb.83.6.1327-1331.1962

Cited by 26 publications

(7 citation statements)

References 5 publications

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“…The ability to oxidize ketosteroids to lactones was detected in fungi of different taxonomic classes, especially: Aspergillus [ 10 – 13 ], Fusarium [ 14 , 15 ] and Penicillium [ 16 – 22 ]. In many transformations, the formation of lactones from 3β-hydroxy-5-ene steroids was accompanied by modification of A-ring occurring through 3β-hydroxy-steroid dehydrogenase/5-ene-4-ene isomerase (3β-HSD) pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Following the earlier reports [ 23 ], it was apparent that cleavage of the pregnane side chain involves four enzymatic reactions: BV oxidation of a substrate to its acetate, hydrolysis of the formed ester to alcohol which is then oxidized to ketone, and oxidative BV lactonization of this ketone to lactone. In transformation of progesterone to testololactone, Sebek and co-workers [ 16 ] have proposed a pathway including 20β-hydroxy-4-pregnen-3-one as an intermediate (Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…1 ). In a number of reports the 20-OH analogues of transformed substrates have been isolated [ 24 – 26 ] and it has been suggested that there exists a competitive equilibrium between the reductase forming this alcohol and the oxidase that regenerates the C-20 ketone [ 16 , 27 , 28 ]. A similar relationship was observed in the oxidation of steroidal C-17 ketones by Beauveria bassiana [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic fate of pregnene-based steroids in the lactonization pathway of multifunctional strain Penicillium lanosocoeruleum

2018

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BackgroundMetabolic activities of microorganisms to modify the chemical structures of organic compounds became an effective tool for the production of high-valued steroidal drugs or their precursors. Currently research efforts in production of steroids of pharmaceutical interest are focused on either optimization of existing processes or identification of novel potentially useful bioconversions. Previous studies demonstrated that P. lanosocoeruleum KCH 3012 metabolizes androstanes to the corresponding lactones with high yield. In order to explore more thoroughly the factors determining steroid metabolism by this organism, the current study was initiated to delineate the specificity of this fungus with respect to the cleavage of steroid side chain of progesterone and pregnenolone The effect of substituents at C-16 in 16-dehydropregnenolone, 16α,17α-epoxy-pregnenolone and 16α-methoxy-pregnenolone on the pattern of metabolic processing of these steroids was also investigated.Results and discussionAll of the analogues tested (except the last of the listed) in multi-step transformations underwent the Baeyer–Villiger oxidation to their δ-d-lactones. The activity of 3β-HSD was a factor affecting the composition of the product mixtures. 16α,17α-epoxy-pregnenolone underwent a rare epoxide opening with retention stereochemistry to give four 16α-hydroxy-lactones. Apart from oxidative transformations, a reductive pathway was revealed with the unique hydrogenation of 5-ene double bond leading to the formation of 3β,16α-dihydroxy-17a-oxa-d-homo-5α-androstan-17-one. 16α-Methoxy-pregnenolone was transformed to the 20(R)-alcohol with no further conversion.ConclusionsThis work clearly demonstrated that P. lanosocoeruleum KCH 3012 has great multi-functional catalytic properties towards the pregnane-type steroids. Studies have highlighted that a slight modification of the d-ring of substrates may control metabolic fate either into the lactonization or reductive and oxidative pathways. Possibility of epoxide opening by enzymes from this microorganism affords a unique opportunity for generation of novel bioactive steroids.Electronic supplementary materialThe online version of this article (10.1186/s12934-018-0948-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic fate of pregnene-based steroids in the lactonization pathway of multifunctional strain Penicillium lanosocoeruleum

2018

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“…However, the compounds differing only by the C-17 function are converted to the same product: 1 as well as 9 yield 3β-hydroxy-17a-oxa- d -homo-androst-5-en-17-one, while 4 , 6, and 8 yield testololactone. Thus, successful BVMO activity requires also effective preceding steps leading to the cleavage or oxidation of the substituent at C-17, which was noted already by Sebek et al [ 43 ].…”

Section: Resultsmentioning

confidence: 80%

Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum

2020

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The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus Penicillium vinaceum AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields.

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“…Sebek et al (22) reported the possibility of 20flhydroxy derivatives (mechanism ii) as intermediates in side-chain degradation of progesterone and lla-hydroxyprogesterone by Penicillium lilacinum. On the other hand, the possibility of a 17a-hydroxy intermediate (mechanism iii) in the oxidative cleavage of the side chain of C2, steroids has precedence in higher organisms (5).…”

mentioning

confidence: 99%

Reduction of the 20-Carbonyl Group of C-21 Steroids by Spores of Fusarium solani and Other Microorganisms. I. Side-Chain Degradation, Epoxide Cleavage, and Substrate Specificity

Plourde

El–Tayeb

Hafez-Zedan

1972

Applied Microbiology

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The spores of Fusarium solani reduced the C20-carbonyl group, 1-dehydrogenated ring "A" and cleaved the side chain of 16a,17a-oxidopregn-4-ene-3,20-dione (16a, 17a-oxidoprogesterone)(I) to give the following products: 20ahydroxy-16a, 17a-oxidopregn-4-en-3-one(II); 20a-hydroxy-16a, 17a-oxidopregna-1,4-dien-3-one(III); 16a-hydroxy-17a-oxa-androsta-1,4-diene-3,17dione (16a-hydroxy-1-dehydrotestololactone)(IV); and 16a,17ft-dihydroxy-androsta-1,4-dien-3-one (16a-hydroxy-1-dehydrotestosterone)(V). When II was used as a substrate, it was metabolized into III, IV, and V at a slower rate than I.

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INTERMEDIATES IN THE METABOLISM OF STEROIDS BY PENICILLIUM LILACINUM

Cited by 26 publications

References 5 publications

Metabolic fate of pregnene-based steroids in the lactonization pathway of multifunctional strain Penicillium lanosocoeruleum

Metabolic fate of pregnene-based steroids in the lactonization pathway of multifunctional strain Penicillium lanosocoeruleum

Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum

Reduction of the 20-Carbonyl Group of C-21 Steroids by Spores of Fusarium solani and Other Microorganisms. I. Side-Chain Degradation, Epoxide Cleavage, and Substrate Specificity

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