Next-generation genetic code expansion.

Next-generation genetic code expansion.
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DOI:
10.1016/j.cbpa.2018.07.020
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发表时间:
2018-10
影响因子:
7.8
通讯作者:
Isaacs FJ
Isaacs FJ
中科院分区:
生物学2区
文献类型:
--
作者:
Arranz-Gibert P;Vanderschuren K;Isaacs FJ

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翻译装置的工程已经允许非标准氨基酸(nsAAs)的位点特异性结合到蛋白质中,从而扩展了生物体的遗传密码。传统的方法集中在将trna和氨基酰基trna合成酶(aaRS)从古细菌移植到细菌和真核生物系统中,在那里它们被设计成特异性编码nsAAs。最近在基因组工程方面的工作开辟了全基因组重新编码的可能性,其中已经构建了具有替代遗传密码的生物体,其中从遗传密码中删除的密码子可以被重新利用为专门用于整合nsAAs的新意义密码子。这些进步,加上工程核糖体和新的分子进化方法的出现,使nsAAs和非天然单体的多位点结合成为可能,为模板定向生产功能化蛋白质、新型聚合物和遗传编码材料铺平了道路。
Engineering of the translation apparatus has permitted the site-specific incorporation of nonstandard amino acids (nsAAs) into proteins, thereby expanding the genetic code of organisms. Conventional approaches have focused on porting tRNAs and aminoacyl-tRNA synthetases (aaRS) from archaea into bacterial and eukaryotic systems where they have been engineered to site-specifically encode nsAAs. More recent work in genome engineering has opened up the possibilities of whole genome recoding, in which organisms with alternative genetic codes have been constructed whereby codons removed from the genetic code can be repurposed as new sense codons dedicated for incorporation of nsAAs. These advances, together with the advent of engineered ribosomes and new molecular evolution methods, enable multisite incorporation of nsAAs and unnatural monomers paving the way for the template-directed production of functionalized proteins, new classes of polymers, and genetically encoded materials.
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