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

Davis, Carol, Carberry, Stephen, Schrettl, Markus , Singh, Ishwar, Stephens, John C., Barry, Sarah M., Kavanagh, Kevin, Challis, Gregory L., 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

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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.

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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