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Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis

Brassinosteroids (BRs) are plant steroid hormones with structural similarity to mammalian sex steroids and ecdysteroids from insects. The BRs are synthesized from sterols and are essential regulators of cell division, cell elongation and cell differentiation. In this work we show that voriconazole,...

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Autores principales: Rozhon, Wilfried, Husar, Sigrid, Kalaivanan, Florian, Khan, Mamoona, Idlhammer, Markus, Shumilina, Daria, Lange, Theo, Hoffmann, Thomas, Schwab, Wilfried, Fujioka, Shozo, Poppenberger, Brigitte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546049/
https://www.ncbi.nlm.nih.gov/pubmed/23335967
http://dx.doi.org/10.1371/journal.pone.0053650
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author Rozhon, Wilfried
Husar, Sigrid
Kalaivanan, Florian
Khan, Mamoona
Idlhammer, Markus
Shumilina, Daria
Lange, Theo
Hoffmann, Thomas
Schwab, Wilfried
Fujioka, Shozo
Poppenberger, Brigitte
author_facet Rozhon, Wilfried
Husar, Sigrid
Kalaivanan, Florian
Khan, Mamoona
Idlhammer, Markus
Shumilina, Daria
Lange, Theo
Hoffmann, Thomas
Schwab, Wilfried
Fujioka, Shozo
Poppenberger, Brigitte
author_sort Rozhon, Wilfried
collection PubMed
description Brassinosteroids (BRs) are plant steroid hormones with structural similarity to mammalian sex steroids and ecdysteroids from insects. The BRs are synthesized from sterols and are essential regulators of cell division, cell elongation and cell differentiation. In this work we show that voriconazole, an antifungal therapeutic drug used in human and veterinary medicine, severely impairs plant growth by inhibiting sterol-14α-demethylation and thereby interfering with BR production. The plant growth regulatory properties of voriconazole and related triazoles were identified in a screen for compounds with the ability to alter BR homeostasis. Voriconazole suppressed growth of the model plant Arabidopsis thaliana and of a wide range of both monocotyledonous and dicotyledonous plants. We uncover that voriconazole toxicity in plants is a result of a deficiency in BRs that stems from an inhibition of the cytochrome P450 CYP51, which catalyzes a step of BR-dependent sterol biosynthesis. Interestingly, we found that the woodland strawberry Fragaria vesca, a member of the Rosaceae, is naturally voriconazole resistant and that this resistance is conferred by the specific CYP51 variant of F. vesca. The potential of voriconazole as a novel tool for plant research is discussed.
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spelling pubmed-35460492013-01-18 Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis Rozhon, Wilfried Husar, Sigrid Kalaivanan, Florian Khan, Mamoona Idlhammer, Markus Shumilina, Daria Lange, Theo Hoffmann, Thomas Schwab, Wilfried Fujioka, Shozo Poppenberger, Brigitte PLoS One Research Article Brassinosteroids (BRs) are plant steroid hormones with structural similarity to mammalian sex steroids and ecdysteroids from insects. The BRs are synthesized from sterols and are essential regulators of cell division, cell elongation and cell differentiation. In this work we show that voriconazole, an antifungal therapeutic drug used in human and veterinary medicine, severely impairs plant growth by inhibiting sterol-14α-demethylation and thereby interfering with BR production. The plant growth regulatory properties of voriconazole and related triazoles were identified in a screen for compounds with the ability to alter BR homeostasis. Voriconazole suppressed growth of the model plant Arabidopsis thaliana and of a wide range of both monocotyledonous and dicotyledonous plants. We uncover that voriconazole toxicity in plants is a result of a deficiency in BRs that stems from an inhibition of the cytochrome P450 CYP51, which catalyzes a step of BR-dependent sterol biosynthesis. Interestingly, we found that the woodland strawberry Fragaria vesca, a member of the Rosaceae, is naturally voriconazole resistant and that this resistance is conferred by the specific CYP51 variant of F. vesca. The potential of voriconazole as a novel tool for plant research is discussed. Public Library of Science 2013-01-15 /pmc/articles/PMC3546049/ /pubmed/23335967 http://dx.doi.org/10.1371/journal.pone.0053650 Text en © 2013 Rozhon et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rozhon, Wilfried
Husar, Sigrid
Kalaivanan, Florian
Khan, Mamoona
Idlhammer, Markus
Shumilina, Daria
Lange, Theo
Hoffmann, Thomas
Schwab, Wilfried
Fujioka, Shozo
Poppenberger, Brigitte
Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title_full Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title_fullStr Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title_full_unstemmed Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title_short Genetic Variation in Plant CYP51s Confers Resistance against Voriconazole, a Novel Inhibitor of Brassinosteroid-Dependent Sterol Biosynthesis
title_sort genetic variation in plant cyp51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546049/
https://www.ncbi.nlm.nih.gov/pubmed/23335967
http://dx.doi.org/10.1371/journal.pone.0053650
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