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Rational design of a biosensor circuit with semi-log dose-response function in Escherichia coli |
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Rational design of a biosensor circuit with semi-log dose-response function in Escherichia coli |
Haoqian Zhang1,2,3, Ying Sheng1, Qianzhu Wu1, Ao Liu1, Yuheng Lu1, Zhenzhen Yin1, Yuansheng Cao3,4, Weiqian Zeng3,4, Qi Ouyang3,4( ) |
1. Peking University Team for the International Genetic Engineering Machine Competition (iGEM), Peking University, Beijng 100871, China; 2. Peking-Tsinghua Joint Center for Life Sciences, School of Life Sciences, Peking University, Beijing 100871, China; 3. Center for Quantitative Biology, Peking University, Beijng 100871, China; 4. State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China |
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Abstract: A central goal of synthetic biology is to apply successful principles that have been developed in electronic and chemical engineering to construct basic biological functional modules, and through rational design, to build synthetic biological systems with predetermined functions. Here, we apply the reverse engineering design principle of biological networks to synthesize a gene circuit that executes semi-log dose-response, a logarithmically linear sensing function, in Escherichia coli cells. We first mathematically define the object function semi-log dose-response, and then search for tri-node network topologies that can most robustly execute the object function. The simplest topology, transcriptional coherent feed-forward loop (TCFL), among the searching results is mathematically analyzed; we find that, in TCFL topology, the semi-log dose-response function arises from the additive effect of logarithmical linearity intervals of Hill functions. TCFL is then genetically implemented in E. coli as a logarithmically linear sensing biosensor for heavy metal ions [mercury (II)]. Functional characterization shows that this rationally designed biosensor circuit works as expected. Through this study we demonstrated the potential application of biological network reverse engineering to broaden the computational power of synthetic biology. |
Key words:
synthetic biology
gene circuit design
reverse engineering
logarithmically linear sensing
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收稿日期: 2013-09-20
出版日期: 2013-09-05
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Corresponding Author(s):
Ouyang Qi,Email:qi@pku.edu.cn
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引用本文: |
. Rational design of a biosensor circuit with semi-log dose-response function in Escherichia coli[J]. Quantitative Biology, 2013, 1(3): 209-220.
Haoqian Zhang, Ying Sheng, Qianzhu Wu, Ao Liu, Yuheng Lu, Zhenzhen Yin, Yuansheng Cao, Weiqian Zeng, Qi Ouyang. Rational design of a biosensor circuit with semi-log dose-response function in Escherichia coli. Quant. Biol., 2013, 1(3): 209-220.
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链接本文: |
https://academic.hep.com.cn/qb/CN/10.1007/s40484-013-0020-4
https://academic.hep.com.cn/qb/CN/Y2013/V1/I3/209
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