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首页> 外文期刊>Applied and Environmental Microbiology >Stress-Responsive Systems Set Specific Limits to the Overproduction of Membrane Proteins in Bacillus subtilis
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Stress-Responsive Systems Set Specific Limits to the Overproduction of Membrane Proteins in Bacillus subtilis

机译：压力响应系统为枯草芽孢杆菌中膜蛋白的过量生产设定了特定限制

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Essential membrane proteins are generally recognized as relevant potential drug targets due to their exposed localization in the cell envelope. Unfortunately, high-level production of membrane proteins for functional and structural analyses is often problematic. This is mainly due to their high overall hydrophobicity. To develop new concepts for membrane protein overproduction, we investigated whether the biogenesis of overproduced membrane proteins is affected by stress response-related proteolytic systems in the membrane. For this purpose, the well-established expression host Bacillus subtilis was used to overproduce eight essential membrane proteins from B. subtilis and Staphylococcus aureus. The results show that the σW regulon (responding to cell envelope perturbations) and the CssRS two-component regulatory system (responding to unfolded exported proteins) set critical limits to membrane protein production in large quantities. The identified sigW or cssRS mutant B. subtilis strains with significantly improved capacity for membrane protein production are interesting candidate expression hosts for fundamental research and biotechnological applications. Importantly, our results pinpoint the interdependent expression and function of membrane-associated proteases as key parameters in bacterial membrane protein production.
机译：由于必需的膜蛋白在细胞膜中的暴露定位，通常被认为是相关的潜在药物靶标。不幸的是，高水平生产用于功能和结构分析的膜蛋白通常是有问题的。这主要是由于它们的高总体疏水性。为了开发膜蛋白过量生产的新概念，我们调查了膜中应力响应相关的蛋白水解系统是否影响了膜过量生产的生物发生。为此目的，已建立的表达宿主枯草芽孢杆菌被用来从枯草芽孢杆菌和金黄色葡萄球菌中过量生产八种必需的膜蛋白。结果表明，σW调节子（响应细胞包膜扰动）和CssRS两组分调节系统（响应未折叠的输出蛋白）为膜蛋白的大量生产设定了关键限值。鉴定出的具有明显提高的膜蛋白生产能力的sigW或cssRS突变体枯草芽孢杆菌菌株是基础研究和生物技术应用的有趣候选表达宿主。重要的是，我们的结果指出了膜相关蛋白酶的相互依赖表达和功能是细菌膜蛋白生产中的关键参数。

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