Functional predictability of universal gene circuits in diverse microbial hosts

Author:

Qin Chenrui1,Xu Tong1,Zhao Xuejin2,Zong Yeqing3,Zhang Haoqian M.3,Lou Chunbo4,Ouyang Qi5,Qian Long5

Affiliation:

1. Peking‐Tsinghua Joint Center for Life Sciences Peking University Beijing China

2. CAS Key Laboratory of Microbial Physiological and Metabolic Engineering Institute of Microbiology Chinese Academy of Sciences Beijing China

3. Bluepha Co., Ltd Beijing China

4. Center for Cell and Gene Circuit Design CAS Key Laboratory of Quantitative Engineering Biology Guangdong Provincial Key Laboratory of Synthetic Genomics Shenzhen Key Laboratory of Synthetic Genomics Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China

5. Center for Quantitative Biology Academy for Advanced Interdisciplinary Studies Peking University Beijing China

Abstract

AbstractAlthough the principles of synthetic biology were initially established in model bacteria, microbial producers, extremophiles and gut microbes have now emerged as valuable prokaryotic chassis for biological engineering. Extending the host range in which designed circuits can function reliably and predictably presents a major challenge for the concept of synthetic biology to materialize. In this work, we systematically characterized the cross‐species universality of two transcriptional regulatory modules—the T7 RNA polymerase activator module and the repressors module—in three non‐model microbes. We found striking linear relationships in circuit activities among different organisms for both modules. Parametrized model fitting revealed host non‐specific parameters defining the universality of both modules. Lastly, a genetic NOT gate and a band‐pass filter circuit were constructed from these modules and tested in non‐model organisms. Combined models employing host non‐specific parameters were successful in quantitatively predicting circuit behaviors, underscoring the potential of universal biological parts and predictive modeling in synthetic bioengineering.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Toward predictable universal genetic circuit design;Quantitative Biology;2024-04-30

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