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 (4). pp. 542-552. ISSN 1074-5521

Full content URL: http://dx.doi.org/10.1016/j.chembiol.2010.12.022

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Item Type:Article
Item Status:Live Archive

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-benzy1-6-hydroxy-1-methoxy-3-methylene-piperazine-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.

Keywords:Biosynthesis
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
ID Code:11294
Deposited On:25 Jul 2013 15:17

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