Functional predictability of universal gene circuits in diverse microbial hosts  

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

机构地区：[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

出　　处：《Quantitative Biology》2024年第2期129-140,共12页定量生物学（英文版）

基　　金：National Natural Science Foundation of China,Grant/Award Number:12090054;National Key Research and Development Programof China,Grant/Award Numbers:2020YFA0906900,2021YFF1200500。

摘　　要：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 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.

关 键 词：circuit predictability host-independent genetic circuits host-nonspecific parameters parts characterization transcriptional regulatory modules 

分 类 号：Q811.4[生物学—生物工程]