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Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum

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. Fu...

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Autores principales: Panek, Anna, Łyczko, Paulina, Świzdor, Alina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570940/
https://www.ncbi.nlm.nih.gov/pubmed/32942593
http://dx.doi.org/10.3390/molecules25184226
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author Panek, Anna
Łyczko, Paulina
Świzdor, Alina
author_facet Panek, Anna
Łyczko, Paulina
Świzdor, Alina
author_sort Panek, Anna
collection PubMed
description 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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spelling pubmed-75709402020-10-28 Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum Panek, Anna Łyczko, Paulina Świzdor, Alina Molecules Article 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. MDPI 2020-09-15 /pmc/articles/PMC7570940/ /pubmed/32942593 http://dx.doi.org/10.3390/molecules25184226 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Panek, Anna
Łyczko, Paulina
Świzdor, Alina
Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title_full Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title_fullStr Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title_full_unstemmed Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title_short Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
title_sort microbial modifications of androstane and androstene steroids by penicillium vinaceum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570940/
https://www.ncbi.nlm.nih.gov/pubmed/32942593
http://dx.doi.org/10.3390/molecules25184226
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