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如何构建合成最小细胞的最小基因组。

How to make a minimal genome for synthetic minimal cell.

机构信息

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Protein Cell. 2010 May;1(5):427-34. doi: 10.1007/s13238-010-0064-4. Epub 2010 Jun 4.

Abstract

As a key focus of synthetic biology, building a minimal artificial cell has given rise to many discussions. A synthetic minimal cell will provide an appropriate chassis to integrate functional synthetic parts, devices and systems with functions that cannot generally be found in nature. The design and construction of a functional minimal genome is a key step while building such a cell/chassis since all the cell functions can be traced back to the genome. Kinds of approaches, based on bioinformatics and molecular biology, have been developed and proceeded to derive essential genes and minimal gene sets for the synthetic minimal genome. Experiments about streamlining genomes of model bacteria revealed genome reduction led to unanticipated beneficial properties, such as high electroporation efficiency and accurate propagation of recombinant genes and plasmids that were unstable in other strains. Recent achievements in chemical synthesis technology for large DNA segments together with the rapid development of the whole-genome sequencing, have transferred synthesis of genes to assembly of the whole genomes based on oligonucleotides, and thus created strong preconditions for synthesis of artificial minimal genome. Here in this article, we review briefly the history and current state of research in this field and summarize the main methods for making a minimal genome. We also discuss the impacts of minimized genome on metabolism and regulation of artificial cell.

摘要

作为合成生物学的一个重点,构建最小的人工细胞引发了许多讨论。一个合成的最小细胞将为整合具有自然中通常不存在的功能的功能性合成部件、设备和系统提供一个合适的底盘。设计和构建功能性最小基因组是构建这样一个细胞/底盘的关键步骤,因为所有的细胞功能都可以追溯到基因组。基于生物信息学和分子生物学的各种方法已经被开发出来,并用于推导合成最小基因组的必需基因和最小基因集。关于简化模式细菌基因组的实验揭示了基因组的减少导致了意想不到的有益特性,例如高电穿孔效率和不稳定在其他菌株中的重组基因和质粒的准确传播。近年来,大 DNA 片段的化学合成技术的进步以及全基因组测序的快速发展,已经将基因的合成转移到基于寡核苷酸的全基因组组装上,从而为人工最小基因组的合成创造了强有力的前提条件。在本文中,我们简要回顾了该领域的历史和研究现状,并总结了构建最小基因组的主要方法。我们还讨论了最小化基因组对人工细胞代谢和调控的影响。

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