title: A dedicated glutathione S-transferase mediates carbon-sulfur bond formation in gliotoxin biosynthesis.
abstract: 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.
authors: Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, 07745 Jena, Germany.
authors: Daniel H
authors: DH
authors: Scharf
authors: Nicole
authors: N
authors: Remme
authors: Andreas
authors: A
authors: Habel
authors: Pranatchareeya
authors: P
authors: Chankhamjon
authors: Kirstin
authors: K
authors: Scherlach
authors: Thorsten
authors: T
authors: Heinekamp
authors: Peter
authors: P
authors: Hortschansky
authors: Axel A
authors: AA
authors: Brakhage
authors: Christian
authors: C
authors: Hertweck
mesh_terms: D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D005912:Gliotoxin / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*
chemical_list: D005912:Gliotoxin; D013455:Sulfur; D002244:Carbon; D005982:Glutathione Transferase