基因组再造与重排构建细胞工厂

doi:10.11949/0438-1157.20190702

摘要/Abstract

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

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

中图分类号:

TQ 033

谢泽雄, 陈祥荣, 肖文海, 李炳志, 元英进. 基因组再造与重排构建细胞工厂[J]. 化工学报, 2019, 70(10): 3712-3721.

Zexiong XIE, Xiangrong CHEN, Wenhai XIAO, Bingzhi LI, Yingjin YUAN. Cell factory construction accelerated by genome synthesis and rearrangement[J]. CIESC Journal, 2019, 70(10): 3712-3721.

图/表 6

图1 底盘细胞与外源代谢路径的适配是细胞工厂构建的核心难题

Fig.1 Adaptability between chassis and heterologous metabolic pathways is key challenge in cell factory construction

图2 基因组人工设计与化学再造可构建柔性底盘细胞

Fig.2 Chassis with flexibilities can be constructed by genome design and synthesis

图3 合成型酿酒酵母SCRaMbLE系统加速基因组重排，产生多样性基因组结构变异

Fig.3 SCRaMbLE system of synthetic yeast accelerates genome rearrangement, generating diverse genomic structural variations

图4 合成型酿酒酵母SCRaMbLE系统快速构建性状优良的底盘细胞

Fig.4 Chassis with excellent traits are constructed rapidly by using SCRaMbLE system of synthetic yeast

图5 合成型酿酒酵母SCRaMbLE系统优化外源代谢路径

Fig.5 Heterologous metabolic pathways can be optimized by SCRaMbLE system of synthetic yeast

图6 合成型酿酒酵母SCRaMbLE系统的精准控制系统(a)与重排菌株文库精准筛选系统(b)

Fig.6 Precise control (a) and identification system (b) for SCRaMbLE in synthetic yeasts

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