A dedicated glutathione S-transferase mediates carbon-sulfur bond formation in gliotoxin biosynthesis.
(2011) A dedicated glutathione S-transferase mediates carbon-sulfur bond formation in gliotoxin biosynthesis. J Am Chem Soc 133(32), 12322-12325.
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.
doi: 10.1021/ja201311d PMID: 21749092