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    The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus


    Davis, Carol and Carberry, Stephen and Schrettl, Markus and Singh, Ishwar and Stephens, John C. and Barry, Sarah M. and Kavanagh, Kevin and Challis, Gregory L. and Brougham, Dermot and Doyle, Sean (2011) The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus. Chemistry and Biology, 18. pp. 542-552. ISSN 1074-5521

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    Abstract

    Gliotoxin, a redox-active metabolite, is produced by the opportunistic fungal pathogen Aspergillus fumigatus, and its biosynthesis is directed by the gli gene cluster. Knowledge of the biosynthetic pathway to gliotoxin, which contains a disulfide bridge of unknown origin, is limited, although L-Phe and L-Ser are known biosynthetic precursors. Deletion of gliG from the gli cluster, herein functionally confirmed as a glutathione S-transferase, results in abrogation of gliotoxin biosynthesis and accumulation of 6-benzyl-6-hydroxy-1-methoxy-3-methylenepiperazine- 2,5-dione. This putative shunt metabolite from the gliotoxin biosynthetic pathway contains an intriguing hydroxyl group at C-6, consistent with a gliotoxin biosynthetic pathway involving thiolation via addition of the glutathione thiol group to a reactive acyl imine intermediate. Complementation of gliG restored gliotoxin production and, unlike gliT, gliG was found not to be involved in fungal self-protection against gliotoxin.

    Item Type: Article
    Additional Information: © 2011 Elsevier Ltd All rights reserved. The definitive version of this article is available at DOI 10.1016/j.chembiol.2010.12.022
    Keywords: Glutathione S-Transferase GliG; Gliotoxin Biosynthesis; Aspergillus fumigatus;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Chemistry
    Item ID: 4087
    Depositing User: Dr. Kevin Kavanagh
    Date Deposited: 22 Jan 2013 15:52
    Journal or Publication Title: Chemistry and Biology
    Publisher: Elsevier (Cell Press)
    Refereed: Yes
    URI:

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