CIESC Journal ›› 2019, Vol. 70 ›› Issue (10): 3712-3721.DOI: 10.11949/0438-1157.20190702

• Reviews and monographs • Previous Articles     Next Articles

Cell factory construction accelerated by genome synthesis and rearrangement

Zexiong XIE1,2(),Xiangrong CHEN1,2,Wenhai XIAO1,2,Bingzhi LI1,2,Yingjin YUAN1,2()   

  1. 1. Frontier Science Center for Synthetic Biology (Ministry of Education), Tianjin 300072, China
    2. Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
  • Received:2019-06-21 Revised:2019-08-31 Online:2019-10-05 Published:2019-10-05
  • Contact: Yingjin YUAN

基因组再造与重排构建细胞工厂

谢泽雄1,2(),陈祥荣1,2,肖文海1,2,李炳志1,2,元英进1,2()   

  1. 1. 教育部合成生物学前沿科学中心,天津 300072
    2. 天津大学化工学院系统生物工程教育部重点实验室,天津 300072
  • 通讯作者: 元英进
  • 作者简介:谢泽雄(1990—),男,博士,副教授,xzx@tju.edu.cn
  • 基金资助:
    国家自然科学基金项目(21621004)

Abstract:

Cell factories can use microbial cells to produce the energy, drugs, and chemicals that humans need. The adaptation of chassis cells to exogenous metabolic pathways is a core challenge in building efficient cell factories. Genome synthesis refers to the bottom-up construction of a genome from chemically synthesized nucleotides. Genomic induced rearrangement refers to the customized regulation of DNA sequences and structures in genome scale. Genome synthesis and inducible rearrangement have enabled the creation of organisms, enhanced the flexibility of model chassis. Proper genome simplification and codon simplification improve the utilization efficiency of substrates and energy, and improve the predictability and controllability of cell physiological performance. Genomic rearrangement can generate structural variations such as random deletion, replication, translocation and inversion. The rearrangements of synthetic genome accelerate the rapid evolution of chassis and the optimization of metabolic pathways, and improve the adaptability between chassis and pathway. The genome synthesis and inducible rearrangement provide a new strategy for the construction and optimization of cell factories.

Key words: genome synthesis, genome rearrangement, cell factory, chassis, metabolic pathway

摘要:

细胞工厂能利用微生物细胞制备人类所需能源、药物和化学品。底盘细胞和外源代谢路径的适配是构建高效细胞工厂的核心难题。基因组再造指利用化学合成的核苷酸分子“自下而上”构建生物基因组,基因组诱导重排指通过在全基因组尺度进行DNA序列与结构的人为调控。基因组再造和诱导重排实现了对生命体的创造,增强了模式底盘细胞的遗传稳定性和操作柔性。基因组的适度精简和密码子简化改善细胞对底物、能量的利用效率,提高细胞生理性能的预测性和可控性。基因组重排可诱导染色体发生随机删除、复制、移位和倒置等结构变异,可产生大量性状优良的模式底盘细胞,进而加速代谢路径优化,提高路径和底盘细胞的适配性,为人工细胞工厂快速构建和优化提供了新策略。

关键词: 基因组再造, 基因组重排, 细胞工厂, 底盘细胞, 代谢路径

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