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Design-build-test of recombinant Bacillus subtilis chassis cell by lifespan engineering for robust bioprocesses

Synthetic and Systems Biotechnology 2024年第3期9卷 470-480页

作者： Kexin Ren Qiang Wang Jianghua Chen Hengwei Zhang Zhoule Guo Meijuan Xu Zhiming Rao Xian Zhang Key Laboratory of Industrial Biotechnology of the Ministry of Education School of BiotechnologyJiangnan UniversityWuxiJiangsu214122China Yixing Institute of Food and Biotechnology Co. LtdYixing214200China

Microbial cell factories utilize renewable raw materials for industrial chemical production,providing a promising path for sustainable *** subtilis is widely used in industry for its food safety properties,but challenges remain in the limitations of microbial *** study proposes a novel strategy based on lifespan engineering to design robust *** chassis cells to supplement traditional metabolic modification strategies that can alleviate cell autolysis,tolerate toxic substrates,and get a higher mass transfer *** modified chassis cells could produce high levels of L-glutaminase,and tolerate hydroquinone to produceα-arbutin *** a 5 L bioreactor,the L-glutaminase enzyme activity of the final strain CRE15TG was increased to 2817.4±21.7 U m L^(-1),about 1.98-fold compared with that of the wild ***α-arbutin yield of strain CRE15A was increased to 134.7 g L^(-1),about 1.34-fold compared with that of the *** our knowledge,both of the products in this study performed the highest yields reported so *** chassis modification strategy described in this study can Improve the utilization efficiency of chassis cells,mitigate the possible adverse effects caused by excessive metabolic modification of engineered strains,and provide a new idea for the future design of microbial cell factories.

关键词： Bacillus subtilis chassis cell Lifespan engineering Robustness Industrial production

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Enabling technology and core theory of synthetic biology

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Science China(Life Sciences) 2023年第8期66卷 1742-1785页

作者： Xian-En Zhang Chenli Liu Junbiao Dai Yingjin Yuan Caixia Gao Yan Feng Bian Wu Ping Wei Chun You Xiaowo Wang Tong Si Faculty of Synthetic Biology Shenzhen Institute of Advanced TechnologyShenzhen 518055China Institute of Synthetic Biology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin 300072China State Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Microbial Metabolism Shanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308China Ministry of Education Key Laboratory of Bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijing 100084China

Synthetic biology provides a new paradigm for life science research(“build to learn”)and opens the future journey of biotechnology(“build to use”).Here,we discuss advances of various principles and technologies in the mainstream of the enabling technology of synthetic biology,including synthesis and assembly of a genome,DNA storage,gene editing,molecular evolution and de novo design of function proteins,cell and gene circuit engineering,cell-free synthetic biology,artificial intelligence(AI)-aided synthetic biology,as well as *** also introduce the concept of quantitative synthetic biology,which is guiding synthetic biology towards increased accuracy and predictability or the real rational *** conclude that synthetic biology will establish its disciplinary system with the iterative development of enabling technologies and the maturity of the core theory.

关键词： synthetic biology quantitative synthetic biology genome synthesis and assembly DNA storage molecular evolution de novo design computer-aided design cell engineering gene circuit chassis cell artificial intelligent(AI) biofoundry

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