The role of glutathione S-transferase GliG in gliotoxin biosynthesis in Aspergillus fumigatus.

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. Copyright © 2011 Elsevier Ltd. All rights reserved.

Citation

Carol Davis, Stephen Carberry, Markus Schrettl, Ishwar Singh, John C Stephens, Sarah M Barry, Kevin Kavanagh, Gregory L Challis, Dermot Brougham, Sean Doyle. The role of glutathione S-transferase GliG in gliotoxin biosynthesis in Aspergillus fumigatus. Chemistry & biology. 2011 Apr 22;18(4):542-52

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PMID: 21513890

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