Manzanares-Miralles, Lara and Bayram, Ozgur and Sarikaya-Bayram, Ozlem and Smith, Elizabeth B. and Dolan, Stephen K. and Jones, Gary W. and Doyle, Sean (2016) Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger. Journal of Proteomics, 131. pp. 149-162. ISSN 1874-3919

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Abstract

Gliotoxin (GT) is a redox-active metabolite, produced by Aspergillus fumigatus,which inhibits the growth of other fungi. Here we demonstrate how Aspergillus niger responds to GT exposure. Quantitative proteomics revealed that GT dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two S-adenosylmethionine (SAM)-dependent methyltransferases. Increased abundance of enzymes S-adenosylhomocysteinase (p = 0.0018) required for homocysteine generation from S-adenosylhomocysteine (SAH), and spermidine synthase (p = 0.0068), involved in the recycling of Met, was observed. Analysis of Met-related metabolites revealed significant increases in the levels of Met and adenosine, in correlation with proteomic data. Methyltransferase MT-II is responsible for bisthiobis(methylthio)gliotoxin (BmGT) formation, deletion of MT-II abolished BmGT formation and led to increased GT sensitivity in A. niger. Proteomic analysis also revealed that GT exposure also significantly (p b 0.05) increased hydrolytic enzyme abundance, including glycoside hydrolases (n = 22) and peptidases (n = 16). We reveal that in an attempt to protect against the detrimental affects of GT, methyltransferase-mediated GT thiomethylation alters cellular pathways involving Met and SAM, with consequential dysregulation of hydrolytic enzyme abundance in A. niger. Thus, it provides new opportunities to exploit the response of GT-naïve fungi to GT.

Item Type:	Article
Keywords:	Mass spectrometry; Aspergillus fumigatus; Methyltransferase; Epigenetics; Glycoside hydrolases; Biofuels;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Institute of Immunology
Item ID:	8160
Identification Number:	https://doi.org/10.1016/j.jprot.2015.10.024
Depositing User:	Ozgur Bayram
Date Deposited:	13 Apr 2017 07:52
Journal or Publication Title:	Journal of Proteomics
Publisher:	Elsevier
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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