建模和测量子使用如何调节在细菌中蛋白质过度表达期间负荷和产量之间的关系
bioRxiv : the preprint server for biology
|December 9, 2024
概括
子优化改善了蛋白质表达,但可能会给细胞带来负担. 过度优化编码子可能会降低蛋白质产量和遗传稳定性,需要细微的策略来更好地设计细胞系统.
科学领域:
- 合成生物学 合成生物学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 过度表达外源蛋白质的细胞负担会影响产量和稳定性.
- 子优化用于提高翻译效率,但其对细胞负担的定量影响尚不清楚.
研究的目的:
- 开发和评估一个静态基因表达模型,量化代码使用偏差和细胞负担之间的关系.
- 为了研究代码子优化如何影响核糖体和tRNA的可用性,并影响本地蛋白质的生产.
主要方法:
- 开发了一个随机基因表达模型,结合了密码子使用偏差,核糖体和tRNA可用性.
- 通过在大肠杆菌中表达sfGFP和mCherry2在各种编码子优化水平上进行实验测试该模型.
主要成果:
- 外源蛋白质表达线性降低了本地蛋白质的产生,而斜率则由代使用匹配调节.
- 确定了一个代过度优化领域,其中增加最佳代使用会使产量和负担恶化.
- 对大肠杆菌的实验结果验证了模型预测,包括过度优化的负面影响.
结论:
- 代码优化策略需要细微化,考虑到过度优化的潜在负面影响.
- 开发的模型为预测和设计改善的蛋白质表达细胞系统提供了一个框架.
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