保存的两组系统CutRS和CssRS控制了Streptomyces中的蛋白质分泌应激反应
Thomas C McLean1,2, Ainsley D M Beaton1,2, Neil A Holmes1,2
1Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom.
mBio
|December 15, 2025
概括
在Streptomyces venezuelae中删除CutRS系统通过绕过葡萄糖抑制来增强生长和抗生素生产. 这种分泌应激感应系统为改善抗生素制造提供了一个新的目标.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 杆菌种类是必需抗生素和其他专门代谢物的丰富生产者.
- 双组件系统调节抗生素的生产,但它们在Streptomyces中的信号机制在很大程度上是未知的.
- CutRS系统是第一个在Streptomyces中发现的双组分系统,之前的研究表明其删除增强了抗生素生产.
研究的目的:
- 为了研究CutRS双组件系统在Streptomyces venezuelae中的功能.
- 阐明CutRS的信号机制和监管目标.
- 探索操纵CutRS以提高抗生素生产的潜力.
主要方法:
- 在Streptomyces venezuelae.中切割RS基因的遗传删除.
- 对增长速度和碳催化剂抑制的分析.
- 调查CutR DNA结合特异性和CutS传感器域突变.
- 通过比较基因组学识别CutR调节子点.
主要成果:
- 删除cutRS增加了生长速度,并逆转了葡萄糖介导的碳催化剂抑制.
- CutR DNA 结合是依赖葡萄糖的,但CutR 没有直接调节生长,新陈代谢或抗生素生物合成基因.
- 在S. coelicolor和S. venezuelae中保存的CutR标是参与分泌应激反应的折叠酶基因 (htrA3,htrB).
- 在CutS传感器域中保存的氨酸残留物中的突变构成性地激活了CutRS系统.
结论:
- 切割RS作为分泌应激传感器,通过在保存的细胞外氨酸残留物中的二硫化键的失效来激活.
- 删除CutRS绕过葡萄糖抑制,导致抗生素过度生产,为工业应用提出了战略.
- CutRS是改善Streptomyces抗生素发现和生产的关键目标.
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