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4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers
The t-type trichothecene producers Fusarium sporotrichioides and Fusarium graminearum protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δtri5 mu...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709292/ https://www.ncbi.nlm.nih.gov/pubmed/34948339 http://dx.doi.org/10.3390/ijms222413542 |
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author | Matsui, Kosuke Takeda, Hirone Shinkai, Koki Kakinuma, Takao Koizumi, Yoshiaki Kase, Masahiro Yoshinari, Tomoya Minegishi, Hiroaki Nakajima, Yuichi Aikawa, Shunichi Takahashi-Ando, Naoko Kimura, Makoto |
author_facet | Matsui, Kosuke Takeda, Hirone Shinkai, Koki Kakinuma, Takao Koizumi, Yoshiaki Kase, Masahiro Yoshinari, Tomoya Minegishi, Hiroaki Nakajima, Yuichi Aikawa, Shunichi Takahashi-Ando, Naoko Kimura, Makoto |
author_sort | Matsui, Kosuke |
collection | PubMed |
description | The t-type trichothecene producers Fusarium sporotrichioides and Fusarium graminearum protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δtri5 mutants expressing all but the first trichothecene pathway enzymes were fed with trichodermol (TDmol), trichothecolone (TCC), 8-deoxytrichothecin, and trichothecin. LC-MS/MS and NMR analyses showed that these C-3 unoxygenated trichothecenes were conjugated with glucose at C-4 by α-glucosidic linkage. As t-type trichothecenes are readily incorporated into the biosynthetic pathway following the C-3 acetylation, the mycotoxins were fed to the ΔFgtri5ΔFgtri101 mutant to examine their fate. LC-MS/MS and NMR analyses demonstrated that the mutant conjugated glucose at C-4 of HT-2 toxin (HT-2) by α-glucosidic linkage, while the ΔFgtri5 mutant metabolized HT-2 to 3-acetyl HT-2 toxin and T-2 toxin. The 4-O-glucosylation of exogenously added t-type trichothecenes appears to be a general response of the ΔFgtri5ΔFgtri101 mutant, as nivalenol and its acetylated derivatives appeared to be conjugated with hexose to some extent. The toxicities of 4-O-glucosides of TDmol, TCC, and HT-2 were much weaker than their corresponding aglycons, suggesting that 4-O-glucosylation serves as a phase II xenobiotic metabolism for t-type trichothecene producers. |
format | Online Article Text |
id | pubmed-8709292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87092922021-12-25 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers Matsui, Kosuke Takeda, Hirone Shinkai, Koki Kakinuma, Takao Koizumi, Yoshiaki Kase, Masahiro Yoshinari, Tomoya Minegishi, Hiroaki Nakajima, Yuichi Aikawa, Shunichi Takahashi-Ando, Naoko Kimura, Makoto Int J Mol Sci Article The t-type trichothecene producers Fusarium sporotrichioides and Fusarium graminearum protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δtri5 mutants expressing all but the first trichothecene pathway enzymes were fed with trichodermol (TDmol), trichothecolone (TCC), 8-deoxytrichothecin, and trichothecin. LC-MS/MS and NMR analyses showed that these C-3 unoxygenated trichothecenes were conjugated with glucose at C-4 by α-glucosidic linkage. As t-type trichothecenes are readily incorporated into the biosynthetic pathway following the C-3 acetylation, the mycotoxins were fed to the ΔFgtri5ΔFgtri101 mutant to examine their fate. LC-MS/MS and NMR analyses demonstrated that the mutant conjugated glucose at C-4 of HT-2 toxin (HT-2) by α-glucosidic linkage, while the ΔFgtri5 mutant metabolized HT-2 to 3-acetyl HT-2 toxin and T-2 toxin. The 4-O-glucosylation of exogenously added t-type trichothecenes appears to be a general response of the ΔFgtri5ΔFgtri101 mutant, as nivalenol and its acetylated derivatives appeared to be conjugated with hexose to some extent. The toxicities of 4-O-glucosides of TDmol, TCC, and HT-2 were much weaker than their corresponding aglycons, suggesting that 4-O-glucosylation serves as a phase II xenobiotic metabolism for t-type trichothecene producers. MDPI 2021-12-17 /pmc/articles/PMC8709292/ /pubmed/34948339 http://dx.doi.org/10.3390/ijms222413542 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matsui, Kosuke Takeda, Hirone Shinkai, Koki Kakinuma, Takao Koizumi, Yoshiaki Kase, Masahiro Yoshinari, Tomoya Minegishi, Hiroaki Nakajima, Yuichi Aikawa, Shunichi Takahashi-Ando, Naoko Kimura, Makoto 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title | 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title_full | 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title_fullStr | 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title_full_unstemmed | 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title_short | 4-O-Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers |
title_sort | 4-o-glucosylation of trichothecenes by fusarium species: a phase ii xenobiotic metabolism for t-type trichothecene producers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709292/ https://www.ncbi.nlm.nih.gov/pubmed/34948339 http://dx.doi.org/10.3390/ijms222413542 |
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