A Dedicated Glutathione S-Transferase Mediates Carbon-Sulfur Bond Formation in Gliotoxin Biosynthesis
A Dedicated Glutathione S-Transferase Mediates Carbon-Sulfur Bond Formation in Gliotoxin Biosynthesis
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DOI：
10.1021/ja201311d
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发表时间：
2011-08-17
影响因子：
15
通讯作者：
Hertweck, Christian
中科院分区：
文献类型：
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作者：
Scharf, Daniel H.;Remme, Nicole;Hertweck, Christian
胶毒素是人类病原体烟曲霉的毒力因子，烟曲霉是侵袭性曲霉病的主要原因。其毒性由epidithiodiketopiperazine（ETP）支架的不寻常的跨环二硫桥介导。在这里，我们公开了一个专门的谷胱甘肽S-转移酶（GST），GliG，在酶促硫化的关键作用。此外，我们表明，双羟化的二酮哌嗪的加氧酶GliC是谷胱甘肽加合物形成的先决条件。这是第一次报道GST参与微生物次级代谢中酶促C-S键形成。
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.