一个专门的谷氨酸S转移酶介导碳硫键的形成在 gliotoxin 生物合成中
Daniel H Scharf1, Nicole Remme, Andreas Habel
1Leibniz Institute for Natural Product Research and Infection Biology, Beutenbergstr. 11a, 07745 Jena, Germany.
Journal of the American Chemical Society
|July 14, 2011
概括
这项研究揭示了GliG,一种谷氨S转移酶 (GST) 如何在Aspergillus fumigatus的关键毒素gliotoxin中产生硫键. 这一发现对于理解侵袭性阿斯伯吉洛症至关重要.
科学领域:
- 微生物学 微生物学
- 菌群学 菌群学 菌群学是指菌群学
- 生物化学 生物化学
背景情况:
- Gliotoxin 是由 Aspergillus fumigatus 产生的主要毒性因子,这是一个常见的人类真菌病原体.
- 侵入性阿斯伯吉洛症是一种严重的真菌感染,通常是由Aspergillus fumigatus引起的.
- Gliotoxin 的毒性归因于其独特的 epidithiodiketopiperazine (ETP) 支架,其特点是跨的二硫化物桥梁.
研究的目的:
- 阐明基质毒素生物合成背后的酶机制.
- 为了确定参与形成关键的二硫化物桥的特定酶在gliotoxin.
- 研究谷氨S转移酶 (GSTs) 在微生物二次新陈代谢中的作用,特别是C-S键的形成.
主要方法:
- 使用纯化的谷氨S转移酶 (GST) GliG的酶分析.
- 氧化酶GliC的生物化学特征及其在基质修饰中的作用.
- 对谷氨添加物形成和C-S键形成的分析.
主要成果:
- 专门的谷氨S转移酶 (GST) GliG在毒素生物合成的酶硫化步骤中发挥着至关重要的作用.
- 由氧化酶GliC对狄基托皮佩拉зин核心的双基化是随后的谷二添加物形成的必要前提.
- 这项研究提供了第一个证据,表明GST参与了微生物二次代谢途径中的催化酶C-S键形成.
结论:
- GliG 对于 gliotoxin 中的跨管二硫化物桥的形成至关重要,这是其毒性机制的一个关键步骤.
- GliC 和 GliG 的顺序作用突显出一种新的 Gliotoxin 成熟和毒性的途径.
- 发现GST参与C-S键形成,为了解真菌的二次新陈代谢和开发有针对性的抗真菌策略开辟了新的途径.
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