In vitro evolution of ribonucleases from expanded genetic alphabets.
In vitro evolution of ribonucleases from expanded genetic alphabets.
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DOI：
10.1073/pnas.2208261119
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发表时间：
2022-11
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
--
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核酸催化反应的能力在生命起源和生物医学应用的背景下是重要的。然而，与蛋白质相比，仅由四个核苷酸构建块组装的标准核酸的催化能力是有限的。使用一个人工扩增的遗传信息系统（AEGIS）携带额外的合成核苷酸，我们表明，DNA库的化学多样性增加，更高的信息密度，更大的可搜索序列空间是至少一个数量级丰富的水库的分子能够催化裂解的RNA比DNA库建立从一个标准的四个核苷酸字母。这里描述的AEGISzyme代表了第一次从扩展的遗传字母构建的文库中进化出催化剂。核酸催化反应（以及存储和传输信息）的能力对基础科学和应用科学都很重要，首先是在分子进化和生命起源的背景下，其次是生物医学应用。然而，与蛋白质相比，仅由四个核苷酸构建块组装的标准核酸（NA）的催化能力是有限的。在这里，我们评估了进化潜力的图书馆的核酸与六个核苷酸的构建块作为水库催化。我们比较了两个核酸文库的RNA切割活性体外选择实验的结果：一个是从标准的四个可独立复制的核苷酸构建的，另一个是从六个构建的，其中两个添加的核苷酸来自人工扩增的遗传信息系统（AEGIS）。从比较实验的结果表明，DNA文库增加化学多样性，更高的信息密度，更大的可搜索序列空间是一个数量级更丰富的水库的分子，催化裂解的磷酸二酯键的RNA比DNA文库建立从一个标准的四个核苷酸字母。具有携带硝基的核碱基Z的进化的AEGISzyme似乎利用一般的酸碱催化机制来切割该键，类似于核糖核酸酶A家族的蛋白酶和重度修饰的DNA酶的机制。这里描述的AEGISzyme代表了一种新型的催化剂，它是从扩展的遗传字母库中进化而来的。
The ability of nucleic acids to catalyze reactions is important in the context of the origin of life and biomedical applications. However, the catalytic power of standard nucleic acids assembled from just four nucleotide building blocks is limited when compared with that of proteins. Using an artificially expanded genetic information system (AEGIS) carrying extra synthetic nucleotides, we show that DNA libraries with increased chemical diversity, higher information density, and larger searchable sequence spaces are at least one order of magnitude richer reservoirs of molecules able to catalyze the cleavage of RNA than DNA libraries built from a standard four-nucleotide alphabet. The AEGISzyme described here represents the first time that catalysts have been evolved from libraries built from expanded genetic alphabets. The ability of nucleic acids to catalyze reactions (as well as store and transmit information) is important for both basic and applied science, the first in the context of molecular evolution and the origin of life and the second for biomedical applications. However, the catalytic power of standard nucleic acids (NAs) assembled from just four nucleotide building blocks is limited when compared with that of proteins. Here, we assess the evolutionary potential of libraries of nucleic acids with six nucleotide building blocks as reservoirs for catalysis. We compare the outcomes of in vitro selection experiments toward RNA-cleavage activity of two nucleic acid libraries: one built from the standard four independently replicable nucleotides and the other from six, with the two added nucleotides coming from an artificially expanded genetic information system (AEGIS). Results from comparative experiments suggest that DNA libraries with increased chemical diversity, higher information density, and larger searchable sequence spaces are one order of magnitude richer reservoirs of molecules that catalyze the cleavage of a phosphodiester bond in RNA than DNA libraries built from a standard four-nucleotide alphabet. Evolved AEGISzymes with nitro-carrying nucleobase Z appear to exploit a general acid–base catalytic mechanism to cleave that bond, analogous to the mechanism of the ribonuclease A family of protein enzymes and heavily modified DNAzymes. The AEGISzyme described here represents a new type of catalysts evolved from libraries built from expanded genetic alphabets.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
21.8
作者：
Chen Z;Lichtor PA;Berliner AP;Chen JC;Liu DR
通讯作者：
Liu DR
影响因子：
56.9
作者：
Johnston, WK;Unrau, PJ;Bartel, DP
通讯作者：
Bartel, DP
影响因子：
8.8
作者：
Futami, Kazunobu;Kimoto, Michiko;Hirao, Ichiro
通讯作者：
Hirao, Ichiro
影响因子：
14.9
作者：
Kaukinen, U;Lyytikäinen, S;Lönnberg, H
通讯作者：
Lönnberg, H