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Construction of Boolean logic gates based on dual-vector circuits of multiple gene regulatory elements

Abstract

Gene circuits are constructed to run complex logical operations for the precise regulation of biological metabolic processes. At present, the implementation of most genetic circuits is based on the regulatory mechanism of various circuit components, but we hope to realize complex logic gates through biological metabolic pathways of organisms. In this study, we matched the regulatory elements of different functional mechanisms to build a Boolean logic gate model by means of a dual-vector circuit. In Escherichia coli, we made 12 circuit logic gate modules and validated the functions of four of the logic gates, including “AND”, “NAND”, “OR” and “NOR” by the expression and analysis of a reporter gene. The inputs were converted into outputs by an intermediate product of the host metabolism. The results indicated that these logic gate circuits had the expected efficacy and regulatory characteristics. Our study provides new ideas for designing genetic circuits and precisely controlling metabolic pathways.

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Acknowledgements

We thank Prof. and Dr. Jin He (State Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, People’s Republic of China) for providing strains pleD and PCMP, as well as Prof. and Dr. Qingsheng Qi (State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, Jinan, People’s Republic of China) for kindly providing strains WMR and lysCfor. In addition, we thank Prof. and Dr. Guifang Dou and assistant, LiyunNiu (Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China), for assistance in detecting c-di-GMP.

Funding

This work was supported by the National Natural Science Foundation of China (Grant 81770857) and the Innovation of special zone project (Grant 1716312ZT00308701).

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Correspondence to Donggang Xu.

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The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants performed by any of the authors.

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Communicated by Dr. Martin Kupiec.

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Wei, Z., Fu, W., Liu, Q. et al. Construction of Boolean logic gates based on dual-vector circuits of multiple gene regulatory elements. Mol Genet Genomics 294, 277–286 (2019). https://doi.org/10.1007/s00438-018-1502-x

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  • DOI: https://doi.org/10.1007/s00438-018-1502-x

Keywords

  • Gene circuit
  • Logic gate
  • Gene regulatory element
  • Precise gene expression regulation