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    Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity


    Smith, Elizabeth B. and Dolan, Stephen K. and Fitzpatrick, David A. and Doyle, Sean and Jones, Gary W. (2016) Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity. Microbial Cell, 3 (3). pp. 120-125. ISSN 2311-2638

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    Abstract

    Gliotoxin (GT) is a mycotoxin produced by some species of asco-mycete fungi including the opportunistic human pathogen Aspergillus fumiga-tus. In order to produce GT the host organism needs to have evolved a self-protection mechanism. GT contains a redox-cycling disulfide bridge that is important in mediating toxicity. Recently is has been demonstrated that A. fumigatus possesses a novel thiomethyltransferase protein called GtmA that has the ability to thiomethylate GT in vivo, which aids the organism in regulating GT biosynthesis. It has been suggested that thiomethylation of GT and similar sulfur-containing toxins may play a role in providing self-protection in host organisms. In this work we have engineered Saccharomyces cerevisiae, a GT-naïve organism, to express A. fumigatus GtmA. We demonstrate that GtmA can readily thiomethylate GT in yeast, which results in protection of the organism from exogenous GT. Our work has implications for understanding the evolution of GT self-protection mechanisms in organisms that are GT pro-ducers and non-producers.

    Item Type: Article
    Additional Information: Cite as: Elizabeth B. Smith, Stephen K. Dolan, David A. Fitzpatrick, Sean Doyle and Gary W. Jones (2016). Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity. Microbial Cell 3(3): 120-125. doi: 10.15698/mic2016.03.485. ©2016 Smith et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
    Keywords: gliotoxin; Aspergillus fumigatus; Saccharomyces cerevisiae; oxidoreductase GliT; thio-methyltransferase GtmA;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 11061
    Identification Number: https://doi.org/10.15698/mic2016.03.485
    Depositing User: David Fitzpatrick
    Date Deposited: 19 Sep 2019 14:13
    Journal or Publication Title: Microbial Cell
    Publisher: Shared Science Publishers
    Refereed: Yes
    URI:
    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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