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@article{Fedoryshchak:2020:10.1039/D0CB00020E,
author = {Fedoryshchak, R and Ocasio, C and Strutton, B and Mattocks, J and Corran, A and Tate, E},
doi = {10.1039/D0CB00020E},
journal = {RSC Chemical Biology},
pages = {68--78},
title = {Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism},
url = {http://dx.doi.org/10.1039/D0CB00020E},
volume = {1},
year = {2020}
}
TY - JOUR
AB - 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.
AU - Fedoryshchak,R
AU - Ocasio,C
AU - Strutton,B
AU - Mattocks,J
AU - Corran,A
AU - Tate,E
DO - 10.1039/D0CB00020E
EP - 78
PY - 2020///
SN - 1747-1613
SP - 68
TI - Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism
T2 - RSC Chemical Biology
UR - http://dx.doi.org/10.1039/D0CB00020E
UR - http://hdl.handle.net/10044/1/79851
VL - 1
ER -
Prof. Ed Tate
GSK Chair in Chemical Biology
Department of Chemistry
Molecular Sciences Research Hub, White City Campus,
82 Wood Lane, London, W12 0BZ
e.tate@imperial.ac.uk
Tel: +44 (0)20 759 + ext 43752 or 45821