基因组设计与合成：从复写到理性设计

汪君仪; 武晓乐; 曹月阳; 李炳志

doi:10.12211/2096-8208.2020-051

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基因组设计与合成：从复写到理性设计

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- 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
- 合成生物学 2021年2卷第2期页码：247-255
- 作者机构：
  
  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
- 作者简介：
  
  [ "汪君仪（1996—），女，博士研究生，研究方向为酿酒酵母基因组设计合成。E-mail：13821492269@163.com" ]
  [ "李炳志（1981—），男，博士，教授，研究方向为合成生物学与生物质生物转化。E-mail：bzli@tju.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“合成生物学”重点专项(2018YFA0900100)
- DOI：10.12211/2096-8208.2020-051
  中图分类号： Q81
- 收稿：2020-06-17，
  
  修回：2020-12-25，
  
  纸质出版：2021-04-30
- 稿件说明：
移动端阅览
汪君仪, 武晓乐, 曹月阳, 李炳志. 基因组设计与合成：从复写到理性设计[J]. 合成生物学, 2021, 2(2): 247-255

WANG Junyi, WU Xiaole, CAO Yueyang, LI Bingzhi. Genome design and synthesis: from replication to rational design[J]. Synthetic Biology Journal, 2021, 2(2): 247-255
汪君仪, 武晓乐, 曹月阳, 李炳志. 基因组设计与合成：从复写到理性设计[J]. 合成生物学, 2021, 2(2): 247-255 DOI： 10.12211/2096-8208.2020-051.

WANG Junyi, WU Xiaole, CAO Yueyang, LI Bingzhi. Genome design and synthesis: from replication to rational design[J]. Synthetic Biology Journal, 2021, 2(2): 247-255 DOI： 10.12211/2096-8208.2020-051.

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。

Abstract

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

gradually making it an effective mean to optimize the host

increase the yield and enhance stress tolerance of the strain. In addition

the prospect of the rational design of genomes and rules for genome simplification is also discussed.

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Keywords

references

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哺乳动物合成基因组学研究进展

基因组的“读-改-写”技术