基因组设计与合成:从复写到理性设计  

Genome design and synthesis:from replication to rational design

作　　者：汪君仪 武晓乐 曹月阳 李炳志[1] WANG Junyi;WU Xiaole;CAO Yueyang;LI Bingzhi(Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education),School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China)

机构地区：[1]教育部合成生物学前沿科学中心,系统生物工程教育部重点实验室,天津大学化工学院,天津300072

出　　处：《合成生物学》2021年第2期247-255,共9页Synthetic Biology Journal

基　　金：真核微生物基因组的人工设计与合成(2018YFA0900100)。

摘　　要：基因组合成相关技术的进步推动人工基因组合成能力不断取得突破,合成基因组学成为了近年来的研究热点,逐步完成了病毒、原核生物基因组的全合成,真核生物基因组设计合成也取得了阶段性突破。在基因组合成的研究过程中,基因组设计的原则不断拓展,基因组设计的尺度由病毒及噬菌体基因组成功复写发展到蕈状支原体JCVI-syn3.0基因组大幅度简化,在真核生物酿酒酵母基因组合成中探索多种基因组设计原则。本文主要综述了人工基因组设计的相关进展,主要内容包括:(1)人工基因组密码子的改变:外源基因密码子的优化,密码子丰度转变原则的探究,大肠杆菌中密码子的删除;(2)人工标签的添加及应用:利用同义密码子替换在合成型基因组中添加标签以区分合成型与野生型基因组;(3)人工位点的添加:酿酒酵母合成型染色体重组系统的开发,优化及应用;(4)基因组简化方面的研究;(5)对基因组理性设计、基因组简化规律挖掘等进行了展望。With the advancement of related technologies for gene assembly,artificial genome assembly capabilities have made breakthroughs continuously,and synthetic genomics has been developed as a research hotspot in recent years.The chemical synthesis of genomes for several viruses and prokaryotes have been completed gradually,and the synthesis of eukaryotic genomes has also been explored.In the study of synthetic genomics,researchers continue to explore principles for genome design and increase its scale and depth,from the successful replication of virus and bacteriophage genomes,the substantial simplification in the Mycoplasma mycoides JCVI-syn3.0 genome to exploring multiple genome design principles in the eukaryotic Saccharomyces cerevisiae.This article summarizes the related progress of artificial genome design,with its main contents focused on:the change of artificial genome codons,the addition of artificial tags,the insertion of artificial sites and the research of genome simplification.In 2016,Church's group used synonymous codons to replace seven codons within the entire genome of E.coli,but the E.coli strain could not survive.In 2019,Chin's research group completed the synthesis of E.coli containing 61 codons using the method of complete genome synthesis,and the E.coli strain can survive normally.Four"watermark"sequences were introduced into the synthetic M.mycoides genome,and a large number of PCR tags were introduced into the synthetic Saccharomyces cerevisiae genome to distinguish between synthetic and wild-type genomes.A highlight of the synthetic yeast chromosome design in the Sc2.0 is the insertion of a reverse symmetric artificial site-loxPsym sequence after the stop codon of each non-essential gene.As a result,a SCRaMbLE(Synthetic Chromosome Rearrangement and Modification by LoxPsym-mediated Evolution)system that can rapidly perform genome rearrangement including deletion,duplication,inversion and translocation was formed in the synthetic yeast.The system has been continuously improved in applications,gr

关 键 词：合成基因组学 基因组设计 密码子删除 合成型标签 SCRAMBLE 基因组简化 

分 类 号：Q81[生物学—生物工程]