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Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism

Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide clas...

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Autores principales: Fedoryshchak, Roman O., Ocasio, Cory A., Strutton, Benjamin, Mattocks, Jo, Corran, Andrew J., Tate, Edward W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: RSC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341946/
https://www.ncbi.nlm.nih.gov/pubmed/34458749
http://dx.doi.org/10.1039/d0cb00020e
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author Fedoryshchak, Roman O.
Ocasio, Cory A.
Strutton, Benjamin
Mattocks, Jo
Corran, Andrew J.
Tate, Edward W.
author_facet Fedoryshchak, Roman O.
Ocasio, Cory A.
Strutton, Benjamin
Mattocks, Jo
Corran, Andrew J.
Tate, Edward W.
author_sort Fedoryshchak, Roman O.
collection PubMed
description Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici.
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spelling pubmed-83419462021-08-26 Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism Fedoryshchak, Roman O. Ocasio, Cory A. Strutton, Benjamin Mattocks, Jo Corran, Andrew J. Tate, Edward W. RSC Chem Biol Chemistry Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici. RSC 2020-05-13 /pmc/articles/PMC8341946/ /pubmed/34458749 http://dx.doi.org/10.1039/d0cb00020e Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Fedoryshchak, Roman O.
Ocasio, Cory A.
Strutton, Benjamin
Mattocks, Jo
Corran, Andrew J.
Tate, Edward W.
Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title_full Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title_fullStr Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title_full_unstemmed Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title_short Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
title_sort wheat pathogen zymoseptoria tritici n-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341946/
https://www.ncbi.nlm.nih.gov/pubmed/34458749
http://dx.doi.org/10.1039/d0cb00020e
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