首页|Functional predictability of universal gene circuits in diverse microbial hosts

Functional predictability of universal gene circuits in diverse microbial hosts

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Although 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 engi-neering.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 charac-terized 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 relation-ships 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 pa-rameters were successful in quantitatively predicting circuit behaviors,underscoring the potential of universal biological parts and predictive modeling in synthetic bioengineering.

circuit predictabilityhost-independent genetic circuitshost-nonspecific parametersparts characterizationtranscriptional regulatory modules

Chenrui Qin、Tong Xu、Xuejin Zhao、Yeqing Zong、Haoqian M.Zhang、Chunbo Lou、Qi Ouyang、Long Qian

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Peking-Tsinghua Joint Center for Life Sciences,Peking University,Beijing,China

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

Bluepha Co.,Ltd,Beijing,China

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

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

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2024

10.1002/qub2.41

定量生物学(英文版)

定量生物学(英文版)

ISSN：
年,卷(期)：2024.12(2)