Peer-Reviewed Journal Details
Mandatory Fields
Davis, C;Carberry, S;Schrettl, M;Singh, I;Stephens, JC;Barry, SM;Kavanagh, K;Challis, GL;Brougham, D;Doyle, S
2011
April
Chemistry and Biology
The Role of Glutathione S-Transferase GliG in Gliotoxin Biosynthesis in Aspergillus fumigatus
Published
46 ()
Optional Fields
NONRIBOSOMAL PEPTIDE SYNTHETASE GENE-CLUSTER LEPTOSPHAERIA-MACULANS MASS-SPECTROMETRY FUNGUS IDENTIFICATION VIRULENCE EXPRESSION NIDULANS CLONING
18
542
552
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.
CAMBRIDGE
1074-5521
10.1016/j.chembiol.2010.12.022
Grant Details