Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, 07745 Jena, Germany.
J Am Chem Soc. 2011 Aug 17;133(32):12322-5. doi: 10.1021/ja201311d. Epub 2011 Jul 22.
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.
曲霉菌烯酮是人类病原体烟曲霉的一种毒力因子，也是侵袭性曲霉菌病的主要病因。其毒性是由独特的跨环二硫键介导的表二硫二肽（ETP）支架。在这里，我们揭示了一种特殊的谷胱甘肽 S-转移酶（GST）GliG 在酶促硫代中的关键作用。此外，我们还表明，双羟化二酮哌嗪由氧化酶 GliC 是形成谷胱甘肽加合物的前提。这是 GST 参与微生物次级代谢中酶促 C-S 键形成的首次报道。
