Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain
- Junran HouJunran HouCAS Key Laboratory of Microbial Physiological and Metabolic Engineering and Institute of Microbiology, State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences, Beijing, 100101, ChinaCollege of Life Science, University of Chinese Academy of Science, Beijing, 100149, ChinaMore by Junran Hou,
- Weiqian ZengWeiqian ZengInstitute of Molecular Precision Medicine, The Xiangya Hospital, Central South University, Changsha, Hunan 410008, P. R. ChinaMore by Weiqian Zeng,
- Yeqing ZongYeqing ZongCAS Key Laboratory of Microbial Physiological and Metabolic Engineering and Institute of Microbiology, State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences, Beijing, 100101, ChinaCollege of Life Science, University of Chinese Academy of Science, Beijing, 100149, ChinaMore by Yeqing Zong,
- Zehua ChenZehua ChenCAS Key Laboratory of Microbial Physiological and Metabolic Engineering and Institute of Microbiology, State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences, Beijing, 100101, ChinaCollege of Life Science, University of Chinese Academy of Science, Beijing, 100149, ChinaMore by Zehua Chen,
- Chensi MiaoChensi MiaoCAS Key Laboratory of Microbial Physiological and Metabolic Engineering and Institute of Microbiology, State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences, Beijing, 100101, ChinaCollege of Life Sciences, University of Science and Technology of China, Hefei, 230027, ChinaMore by Chensi Miao,
- Baojun WangBaojun WangSchool of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FF, U.K.Centre for Synthetic and System Biology, University of Edinburgh, Edinburgh, EH9 3FF, U.K.More by Baojun Wang, and
- Chunbo Lou*Chunbo Lou*Tel.: +86-10-6480 6105. E-mail: [email protected]CAS Key Laboratory of Microbial Physiological and Metabolic Engineering and Institute of Microbiology, State Key Laboratory of Microbial Resources, Institute of Microbiology Chinese Academy of Sciences, Beijing, 100101, ChinaCollege of Life Sciences, University of Science and Technology of China, Hefei, 230027, ChinaCollege of Life Science, University of Chinese Academy of Science, Beijing, 100149, ChinaMore by Chunbo Lou
Abstract
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.
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