Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P. R. China.
Singapore Institute of Food and Biotechnology Innovation, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, 138669, Singapore.
Chembiochem. 2022 Nov 4;23(21):e202200295. doi: 10.1002/cbic.202200295. Epub 2022 Sep 22.
Naturally occurring DNA contains four canonical bases, forming two Watson-Crick base pairs (adenine-thymine, guanine-cytosine). Efforts over the past decades have led to the development of several unnatural base pairs, enabling the synthesis of unnatural DNA with an expanded genetic alphabet. The engineering of organisms capable of de novo biosynthesis of unnatural DNA would have significant technological and philosophical implications, but remains a challenge. Here we report the enzymatic conversion of 2'-deoxyxanthosine 5'-monophosphate (dXMP) into deoxyisoguanosine monophosphate (dBMP), a precursor of the unnatural isoguanine-isocytosine base pair. The reaction is catalyzed by the bacteriophage enzyme PurZ and bacterial PurB, and is a key addition to the toolbox for de novo biosynthesis of unnatural DNA.
天然存在的 DNA 包含四个经典碱基，形成两个 Watson-Crick 碱基对（腺嘌呤-胸腺嘧啶，鸟嘌呤-胞嘧啶）。过去几十年来的努力导致了几种非天然碱基对的发展，使具有扩展遗传字母表的非天然 DNA 的合成成为可能。能够从头合成非天然 DNA 的生物体的工程化具有重大的技术和哲学意义，但仍然是一个挑战。在这里，我们报告了 2'-脱氧黄嘌呤核苷 5'-单磷酸（dXMP）转化为脱氧异鸟嘌呤单磷酸（dBMP）的酶促反应，dBMP 是非天然异鸟嘌呤-异胞嘧啶碱基对的前体。该反应由噬菌体酶 PurZ 和细菌 PurB 催化，是从头合成非天然 DNA 的工具包的重要补充。
