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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Main Authors: Wilfried Rozhon, Sigrid Husar, Florian Kalaivanan, Mamoona Khan, Markus Idlhammer, Daria Shumilina, Theo Lange, Thomas Hoffmann, Wilfried Schwab, Shozo Fujioka, Brigitte Poppenberger
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0053650&type=printable
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author Wilfried Rozhon
Sigrid Husar
Florian Kalaivanan
Mamoona Khan
Markus Idlhammer
Daria Shumilina
Theo Lange
Thomas Hoffmann
Wilfried Schwab
Shozo Fujioka
Brigitte Poppenberger
author_facet Wilfried Rozhon
Sigrid Husar
Florian Kalaivanan
Mamoona Khan
Markus Idlhammer
Daria Shumilina
Theo Lange
Thomas Hoffmann
Wilfried Schwab
Shozo Fujioka
Brigitte Poppenberger
author_sort Wilfried Rozhon
collection DOAJ
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 doaj-art-87ed7f749f8a444382ce240a12dd58d42025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5365010.1371/journal.pone.0053650Genetic variation in plant CYP51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis.Wilfried RozhonSigrid HusarFlorian KalaivananMamoona KhanMarkus IdlhammerDaria ShumilinaTheo LangeThomas HoffmannWilfried SchwabShozo FujiokaBrigitte PoppenbergerBrassinosteroids (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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0053650&type=printable
spellingShingle Wilfried Rozhon
Sigrid Husar
Florian Kalaivanan
Mamoona Khan
Markus Idlhammer
Daria Shumilina
Theo Lange
Thomas Hoffmann
Wilfried Schwab
Shozo Fujioka
Brigitte Poppenberger
Genetic variation in plant CYP51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0053650&type=printable
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