title: Towards understanding the gliotoxin detoxification mechanism:in vivothiomethylation protects yeast from gliotoxin cytotoxicity.
abstract: Gliotoxin (GT) is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogenAspergillus fumigatus. 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 thatA. fumigatuspossesses a novel thiomethyltransferase protein called GtmA that has the ability to thiomethylate GTin 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 engineeredSaccharomyces cerevisiae, a GT-naïve organism, to expressA. fumigatusGtmA. 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 producers and non-producers.
authors.affiliation: Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Smith
authors.affiliation: Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Dolan
authors.affiliation: Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.
authors.forename: David A
authors.initials: DA
authors.lastname: Fitzpatrick
authors.affiliation: Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Doyle
authors.affiliation: Department of Biology, Maynooth University, Maynooth, County Kildare, Ireland.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
keywords: Aspergillus fumigatus; Saccharomyces cerevisiae; gliotoxin; oxidoreductase GliT; thio-methyltransferase GtmA