A Dedicated Glutathione S-Transferase Mediates Carbon–Sulfur Bond Formation in Gliotoxin Biosynthesis

Gliotoxin is a virulence factor of the human pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Its toxicity is mediated by the unusual transannular disulfide bridge of the epidithiodiketopiperazine (ETP) scaffold. Here we disclose the critical role of a specialized glutath...

Full description

Saved in:
Bibliographic Details
Published inJournal of the American Chemical Society Vol. 133; no. 32; pp. 12322 - 12325
Main Authors Scharf, Daniel H, Remme, Nicole, Habel, Andreas, Chankhamjon, Pranatchareeya, Scherlach, Kirstin, Heinekamp, Thorsten, Hortschansky, Peter, Brakhage, Axel A, Hertweck, Christian
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 17.08.2011
Amer Chemical Soc
Subjects
Aspergillus fumigatus - enzymology
Aspergillus fumigatus - metabolism
Carbon - metabolism
Chemistry
Chemistry, Multidisciplinary
Gliotoxin - metabolism
Glutathione Transferase - metabolism
Physical Sciences
Science & Technology
Sulfur - metabolism
SYSTEM
ASPERGILLUS-FUMIGATUS
NONRIBOSOMAL PEPTIDE SYNTHETASE
FUNGUS
GENE
GLIP
Online AccessGet full text

Cover

More Information
Summary:Gliotoxin is a virulence factor of the human pathogen Aspergillus fumigatus, the leading cause of invasive aspergillosis. Its toxicity is mediated by the unusual transannular disulfide bridge of the epidithiodiketopiperazine (ETP) scaffold. Here we disclose the critical role of a specialized glutathione S-transferase (GST), GliG, in enzymatic sulfurization. Furthermore, we show that bishydroxylation of the diketopiperazine by the oxygenase GliC is a prerequisite for glutathione adduct formation. This is the first report of the involvement of a GST in enzymatic C–S bond formation in microbial secondary metabolism.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja201311d