美国麻省理工学院Ron Weiss小组开发出一种工程化的蛋白质磷酸化切换网络。该研究于2021年7月2日发表于国际一流学术期刊《科学》。

研究人员使用包含11个蛋白质-蛋白质磷酸化元件的交叉抑制拓扑在酿酒酵母中创建了一个双稳态切换键开关。这个切换键是超灵敏的，可以在几秒钟内被诱导切换状态，并表现出长期的双稳态。受这个切换键结构和大小的启发，研究人员开发了一个计算框架来搜索其他大型和类似双稳态网络的内源性蛋白质通路。

这个框架帮助研究人员识别并通过实验验证了五个以前未报告的表现出双稳态的内源网络。构建合成蛋白质-蛋白质网络将使生物工程师能够设计快速传感和处理系统，从而实现对细胞过程进行复杂的调节，并有助于发现具有特定功能的内源性网络。

据悉，包含快速、可逆反应的合成生物网络可以设计新的细胞行为，而这些行为在较慢的调节下是不可能的。

附：英文原文

Title: An engineered protein-phosphorylation toggle network with implications for endogenous network discovery

Author: Deepak Mishra, Tristan Bepler, Brian Teague, Bonnie Berger, Jim Broach, Ron Weiss

Issue&Volume: 2021/07/02

Abstract: Synthetic biological networks comprising fast, reversible reactions could enable engineering of new cellular behaviors that are not possible with slower regulation. Here, we created a bistable toggle switch in Saccharomyces cerevisiae using a cross-repression topology comprising 11 protein-protein phosphorylation elements. The toggle is ultrasensitive, can be induced to switch states in seconds, and exhibits long-term bistability. Motivated by our toggle’s architecture and size, we developed a computational framework to search endogenous protein pathways for other large and similar bistable networks. Our framework helped us to identify and experimentally verify five formerly unreported endogenous networks that exhibit bistability. Building synthetic protein-protein networks will enable bioengineers to design fast sensing and processing systems, allow sophisticated regulation of cellular processes, and aid discovery of endogenous networks with particular functions.

DOI: 10.1126/science.aav0780

Source: https://science.sciencemag.org/content/373/6550/eaav0780