A Dedicated Glutathione 5-Transferase Mediates Carbon-Sulfur Bond Formation in Gliotoxin Biosynthesis

摘要

Gliotoxin is a virulence factor of the human pathogen Aspergillusfumigatus, the leading cause of invasive aspergillosis. Its toxicity is mediated by the unusual transan-nular 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 bishydrox-ylation 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.