Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Nat Commun. 2021 Feb 5;12(1):804. doi: 10.1038/s41467-021-21128-0.
Evolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclic L-threoninol nucleic acid (L-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an L-aTNA fragment on an L-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both L-aTNA ligation on a DNA template and DNA ligation on an L-aTNA template are also observed. High efficiency ligation of trimer L-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random L-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the L-aTNA world.
Xeno 核酸 (XNA) 世界的进化本质上需要模板指导的 XNA 聚合物合成。在这项研究中，我们通过 N-氰基咪唑介导的化学连接证明了非循环 XNA，非循环 L-苏氨酸核酸 (L-aTNA) 的模板指导合成。L-aTNA 片段在 L-aTNA 模板上的连接比 DNA 连接快得多，产率也高得多。还观察到 DNA 模板上的 L-aTNA 连接和 L-aTNA 模板上的 DNA 连接。实现了三聚体 L-aTNA 片段与模板结合引物的高效连接。此外，还使用随机 L-aTNA 三聚体作为底物证明了拟引物延伸反应。据我们所知，这是首例使用所有四个碱基的 XNA 聚合酶样引物延伸的例子，在没有任何特殊修饰的情况下生成磷酸二酯键。这项技术为 L-aTNA 世界的遗传系统铺平了道路。
