工程直角信号通道揭示了序列空间的稀疏占用
Conor J McClune1,2, Aurora Alvarez-Buylla1, Christopher A Voigt2
1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature
|October 25, 2019
概括
研究人员通过设计功能性酶基质对,在大肠杆菌中创造了新的信号通路. 这表明序列空间不拥挤,允许简单的进化或新的绝缘细胞路径的设计.
科学领域:
- 分子生物学
- 合成生物学
- 系统生物学
背景情况:
- 基因重复会创建新的信号通路, 但需要隔离来防止交叉通话.
- 工程新途径或在基因组之间转移它们面临着由于现有的相似性而带来的挑战.
- 导入途径的容易性取决于序列空间中的对应密度,由特异性决定的残留物定义.
研究的目的:
- 在序列空间中研究对等路径的密度和分布.
- 在大肠杆菌中产生新型,隔离的两组合信号通路.
- 评估直角信号通路的新设计潜力.
主要方法:
- 使用细胞分类与深度测序分析大型工程蛋白质库.
- 基于共同进化的图书馆来生成新的酶基质对.
- 对大肠杆菌中现有的路径进行正交路径测试.
主要成果:
- 成功产生了58个具有新奇酶基质特异性的绝缘通路.
- 证明了几条新路径与现有的27条大肠杆菌路径是正交的.
- 识别了六个相互直角的酶基质对,增加了信号传输能力.
结论:
- 序列空间并没有被类似路径密集占用.
- 这种稀疏性表明新的绝缘通道可以很容易地演变或重新设计.
- 成功设计了一种对植物细胞因子反应的新途径,
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