De novo design of an intercellular signaling toolbox for multi-channel cell–cell communication and biological computation

Pei Du, Huiwei Zhao, Haoqian Zhang, Ruisha Wang, Jianyi Huang, Ye Tian, Xudong Luo, Xunxun Luo, Min Wang, Yanhui Xiang, Long Qian, Yihua Chen, Yong Tao () and Chunbo Lou ()
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Pei Du: Chinese Academy of Sciences
Huiwei Zhao: Chinese Academy of Sciences
Haoqian Zhang: Bluepha Co., Ltd
Ruisha Wang: Chinese Academy of Sciences
Jianyi Huang: Chinese Academy of Sciences
Ye Tian: Chinese Academy of Sciences
Xudong Luo: Chinese Academy of Sciences
Xunxun Luo: Chinese Academy of Sciences
Min Wang: Chinese Academy of Sciences
Yanhui Xiang: Chinese Academy of Sciences
Long Qian: Peking University
Yihua Chen: Chinese Academy of Sciences
Yong Tao: Chinese Academy of Sciences
Chunbo Lou: University of Chinese Academy of Science

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design a genetic toolbox for high-performance, multi-channel cell–cell communications and biological computations. By biosynthetic pathway design for signal molecules, rational engineering of sensing promoters and directed evolution of sensing transcription factors, we obtain six cell–cell signaling channels in bacteria with orthogonality far exceeding the conventional quorum sensing systems and successfully transfer some of them into yeast and human cells. For demonstration, they are applied in cell consortia to generate bacterial colony-patterns using up to four signaling channels simultaneously and to implement distributed bio-computation containing seven different strains as basic units. This intercellular signaling toolbox paves the way for engineering complex multicellularity including artificial ecosystems and smart tissues.

Date: 2020
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DOI: 10.1038/s41467-020-17993-w

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