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The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans

The fungus Cunninghamella elegans is recognised as a microbial model of mammalian drug metabolism owing to its ability to catabolise xenobiotic compounds in an analogous fashion to animals. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activ...

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Autores principales: Palmer-Brown, William, Miranda-CasoLuengo, Raúl, Wolfe, Kenneth H., Byrne, Kevin P., Murphy, Cormac D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592952/
https://www.ncbi.nlm.nih.gov/pubmed/31239505
http://dx.doi.org/10.1038/s41598-019-45706-x
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author Palmer-Brown, William
Miranda-CasoLuengo, Raúl
Wolfe, Kenneth H.
Byrne, Kevin P.
Murphy, Cormac D.
author_facet Palmer-Brown, William
Miranda-CasoLuengo, Raúl
Wolfe, Kenneth H.
Byrne, Kevin P.
Murphy, Cormac D.
author_sort Palmer-Brown, William
collection PubMed
description The fungus Cunninghamella elegans is recognised as a microbial model of mammalian drug metabolism owing to its ability to catabolise xenobiotic compounds in an analogous fashion to animals. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activity; however, almost nothing is known about these enzymes in the fungus. In this paper we report the in silico analysis of the genome sequence of C. elegans B9769, which contains 32 genes putatively coding for CYPs. Based on their predicted amino acid sequences these were classified as belonging to CYP509, 5203, 5208, 5313, 5210, 61 and 51 families. Reverse transcription-quantitative PCR revealed that the gene coding for CYP5313D1 was significantly upregulated when C. elegans DSM1908 was cultivated in sabouraud dextrose in contrast to its expression in cells grown in Roswell Park Memorial Institute medium. This corresponded to the fungus’ xenobiotic biotransformation ability when grown in the two media. Heterologous expression of cyp5313D1 in Pichia pastoris resulted in a recombinant strain that biotransformed flurbiprofen to 4′-hydroxyflurbiprofen, the same metabolite generated by C. elegans cultures. This is the first report of a xenobiotic-biotransforming CYP from this biotechnologically important fungus.
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spelling pubmed-65929522019-07-03 The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans Palmer-Brown, William Miranda-CasoLuengo, Raúl Wolfe, Kenneth H. Byrne, Kevin P. Murphy, Cormac D. Sci Rep Article The fungus Cunninghamella elegans is recognised as a microbial model of mammalian drug metabolism owing to its ability to catabolise xenobiotic compounds in an analogous fashion to animals. Its ability to produce phase I (oxidative) metabolites of drugs is associated with cytochrome P450 (CYP) activity; however, almost nothing is known about these enzymes in the fungus. In this paper we report the in silico analysis of the genome sequence of C. elegans B9769, which contains 32 genes putatively coding for CYPs. Based on their predicted amino acid sequences these were classified as belonging to CYP509, 5203, 5208, 5313, 5210, 61 and 51 families. Reverse transcription-quantitative PCR revealed that the gene coding for CYP5313D1 was significantly upregulated when C. elegans DSM1908 was cultivated in sabouraud dextrose in contrast to its expression in cells grown in Roswell Park Memorial Institute medium. This corresponded to the fungus’ xenobiotic biotransformation ability when grown in the two media. Heterologous expression of cyp5313D1 in Pichia pastoris resulted in a recombinant strain that biotransformed flurbiprofen to 4′-hydroxyflurbiprofen, the same metabolite generated by C. elegans cultures. This is the first report of a xenobiotic-biotransforming CYP from this biotechnologically important fungus. Nature Publishing Group UK 2019-06-25 /pmc/articles/PMC6592952/ /pubmed/31239505 http://dx.doi.org/10.1038/s41598-019-45706-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Palmer-Brown, William
Miranda-CasoLuengo, Raúl
Wolfe, Kenneth H.
Byrne, Kevin P.
Murphy, Cormac D.
The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title_full The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title_fullStr The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title_full_unstemmed The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title_short The CYPome of the model xenobiotic-biotransforming fungus Cunninghamella elegans
title_sort cypome of the model xenobiotic-biotransforming fungus cunninghamella elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592952/
https://www.ncbi.nlm.nih.gov/pubmed/31239505
http://dx.doi.org/10.1038/s41598-019-45706-x
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