From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma.

From polymerase engineering to semi-synthetic life: artificial expansion of the central dogma.
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DOI:
10.1039/d2cb00116k
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发表时间:
2022-10-05
影响因子:
4.1
通讯作者:
Chen, Tingjian
Chen, Tingjian
中科院分区:
其他
文献类型:
--
作者:
Sun, Leping;Ma, Xingyun;Zhang, Binliang;Qin, Yanjia;Ma, Jiezhao;Du, Yuhui;Chen, Tingjian

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在过去的几十年里,核酸在不同的部分中被广泛修饰,以扩大遗传物质的范围。虽然非天然碱基对(UBP)的发展扩大了核酸的遗传信息容量,但DNA和RNA的合成替代物的产生增加了遗传信息载体的类型,并将新的性质和功能引入核酸。此外,将DNA聚合酶(DNAP)和RNA聚合酶(RNAP)定制为有效的非天然核酸聚合酶的努力已经使得这些非天然核酸能够广泛应用,范围从稳定适体的产生到新型催化剂的进化。将非天然核酸引入活的生物体中也开始扩展体内的中心法则。在这篇文章中,我们首先总结了非天然核酸的发展与修饰或改变在不同的部分。工程DNAP和RNAP的策略进行了广泛的审查,然后总结了主要的聚合酶突变体具有良好的活性,合成,逆转录,甚至扩增非天然核酸。介绍了近年来非天然核酸及其聚合酶的应用实例。最后,综述了将UBPs和人工合成的遗传聚合物引入生物体以创造半合成生物体的方法。在过去的几十年中,核酸在不同的部分中被广泛修饰以扩大遗传物质的范围,并且工程化的聚合酶极大地促进了它们在体外和体内的应用。
Nucleic acids have been extensively modified in different moieties to expand the scope of genetic materials in the past few decades. While the development of unnatural base pairs (UBPs) has expanded the genetic information capacity of nucleic acids, the production of synthetic alternatives of DNA and RNA has increased the types of genetic information carriers and introduced novel properties and functionalities into nucleic acids. Moreover, the efforts of tailoring DNA polymerases (DNAPs) and RNA polymerases (RNAPs) to be efficient unnatural nucleic acid polymerases have enabled broad application of these unnatural nucleic acids, ranging from production of stable aptamers to evolution of novel catalysts. The introduction of unnatural nucleic acids into living organisms has also started expanding the central dogma in vivo. In this article, we first summarize the development of unnatural nucleic acids with modifications or alterations in different moieties. The strategies for engineering DNAPs and RNAPs are then extensively reviewed, followed by summarization of predominant polymerase mutants with good activities for synthesizing, reverse transcribing, or even amplifying unnatural nucleic acids. Some recent application examples of unnatural nucleic acids with their polymerases are then introduced. At the end, the approaches of introducing UBPs and synthetic genetic polymers into living organisms for the creation of semi-synthetic organisms are reviewed and discussed. Nucleic acids have been extensively modified in different moieties to expand the scope of genetic materials in the past few decades, and engineered polymerases greatly facilitate their application in vitro and in vivo.
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