Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain,ACS Synthetic Biology

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Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-05-07 00:00:00 , DOI: 10.1021/acssynbio.7b00414
Junran Hou _{1,

2} , Weiqian Zeng ₃ , Yeqing Zong _{1,

2} , Zehua Chen _{1,

2} , Chensi Miao _{1,

4} , Baojun Wang _{5,

6} , Chunbo Lou _{1,

2,

4}

Affiliation

The dimerization and high-order oligomerization of transcription factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of transcription factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a transcription factor for the regulated promoter. Then, seven additional transcription factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that the engineered ultrasensitive transcription factor could be used to significantly improve the performance of a “stripe-forming” gene circuit. We envision that the oligomerization modules engineered in this study could act as a powerful tool to rapidly tune the underlying response profiles of synthetic gene circuits and metabolic pathway controllers.

中文翻译：

通过融合模块寡聚化域工程化超敏转录因子

转录因子的二聚化和高阶寡聚化赋予了它们协同调节功能，这些调节功能在许多细胞功能中起着重要作用。但是，这种先进的调节能力尚未在合成生物学和基因工程中得到充分利用。在这里，我们设计了一个C末端融合的寡聚域，以提高转录因子的协同作用。首先，我们发现三个设计的低聚结构域中的两个显着增加了转录因子对受调控启动子的协同作用和超敏感性。然后，使用七个额外的转录因子来评估寡聚化域的模块性，并且通过其希尔系数来评估它们的超敏性通常会得到改善。而且，我们还证明了当与设计的寡聚化域融合时，配体响应域的变构能力仍保持不变。作为一个示例应用程序，我们证明了工程化的超敏转录因子可用于显着改善“条带形成”基因电路的性能。我们预想，这项研究中设计的低聚模块可以作为快速调节合成基因电路和代谢途径控制器的潜在反应模式的有力工具。

更新日期：2018-05-07

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