增强N-甲基氨基酸融入蛋白质和,使用修改的细菌核糖体和延长因子P
Chao Zhang1, Shengxi Chen1, Xuan Fu1
1Biodesign Center for BioEnergetics, Arizona State University, Tempe, Arizona 85287, United States.
ACS chemical biology
|May 20, 2024
概括
研究人员开发了新的核糖体策略,将N-甲基化氨基酸纳入和蛋白质中. 修改后的核糖体和EF-P补充剂提高了产量,使这些修改后的生物分子能够得到更广泛的应用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 合成生物学 合成生物学
背景情况:
- N-甲基化氨基酸是天然生物活性和蛋白质的关键组成部分,影响其构成和稳定性.
- 虽然化学合成,但生产N-甲基化的核糖体策略正在出现.
- 了解核糖体结合机制是扩大和蛋白质合成工具包的关键.
研究的目的:
- 开发用于将N-甲基化氨基酸结合到和蛋白质的新策略.
- 为了确定修改后的核糖体和辅助因素,以促进这一过程.
- 研究N-甲基化对和蛋白质合成产量的影响.
主要方法:
- 能够结合六种N-甲基化氨基酸的修饰核糖体的识别和表征.
- 使用这些修饰的核糖体,合成一种抗菌 (IsCT) 和一种蛋白质域 (RRM1).
- 计算建模以了解核糖体结构适应N-甲基化氨基酸结合的结构性适应.
- 用细菌延长因子P (EF-P) 补充,以提高产量.
主要成果:
- 成功将六种N-甲基化氨基酸结合到ISCT和RRM1.1.的核糖体中.
- 使用修改后的核糖体,对大多数测试的N-甲基化氨基酸的合成产量得到了改善.
- 计算模型揭示了23SrRNA中的补偿性核酸变化.
- 补充EF-P进一步提高了几个N-甲基化氨基酸的产量.
结论:
- 新的核糖体策略使和蛋白质与N-甲基化氨基酸的合成成为可能.
- 改性核糖体和EF-P是克服与核糖体合成期间N-甲基化相关的挑战的关键因素.
- 这些进步扩大了生产具有量身定制属性的N-甲基化和蛋白质的潜力.
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