DNA-editing enzymes perform chemical reactions on DNA nucleobases. These reactions can change the genetic identity of the modified base or modulate gene expression. Interest in DNA-editing enzymes has burgeoned in recent years due to the advent of clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) systems, which can be used to direct their DNA-editing activity to specific genomic loci of interest. In this review, we showcase DNA-editing enzymes that have been repurposed or redesigned and developed into programmable base editors. These include deaminases, glycosylases, methyltransferases, and demethylases. We highlight the astounding degree to which these enzymes have been redesigned, evolved, and refined and present these collective engineering efforts as a paragon for future efforts to repurpose and engineer other families of enzymes. Collectively, base editors derived from these DNA-editing enzymes facilitate programmable point mutation introduction and gene expression modulation by targeted chemical modification of nucleobases.

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DNA编辑酶作为碱基编辑器的设计与应用

DNA 编辑酶对 DNA 核碱基进行化学反应。这些反应可以改变修饰碱基的遗传特性或调节基因表达。近年来，由于成簇规则间隔短回文重复相关 (CRISPR-Cas) 系统的出现，人们对 DNA 编辑酶的兴趣日益浓厚，该系统可用于将 DNA 编辑活性定向到特定的感兴趣的基因组位点。在这篇综述中，我们展示了经过重新调整用途或重新设计并开发成可编程碱基编辑器的 DNA 编辑酶。这些酶包括脱氨酶、糖基化酶、甲基转移酶和脱甲基酶。我们强调这些酶被重新设计、进化和完善的惊人程度，并将这些集体工程努力作为未来重新利用和工程其他酶家族的努力的典范。总的来说，源自这些 DNA 编辑酶的碱基编辑器通过核碱基的靶向化学修饰促进可编程点突变引入和基因表达调节。