Abstract:

On April 30, 2021, three Z-genome research papers were published in Science. This article will comment on the collaborative work performed at laboratories led by Zhao Suwen at Shanghai Technology University, Zhang Yan at Tianjin University, and Zhao Huimin at University of Illinois at Urbana-Champaign and Agency for Science, Technology and Research (A*STAR) Singapore. First, we introduce the multi-enzyme system mediated Z-genome biosynthesis. Then we address the discovery of dATPase and DUF550 that reduce the concentration of dATP in the host bacteria. Finally, we highlight the sequencing and identification of the Z-genome and its functional significance. Forty-four years ago, Soviet scientists discovered for the first time that diaminopurine (Z) was presented in the DNA of Cyanophage S-2L. Z is a modified unique base that replaces adenine (A), which form three hydrogen bonds with thymine (T), but the biosynthetic pathway of the Z-genome had been an unsolved mystery for the past decades. Very recently, the multi-enzyme system to biosynthesize Z-genome has been characterized by various methods including bioinformatics, computational biology and biochemistry methods through collaborations among Professors Zhao Suwen, Zhang Yan and Zhao Huimin. They concluded that this pathway exists in dozens of phages distributed around the world, including Acinetobacter phage SH-Ab 15497, which was discovered and isolated in Shanghai. The team used HPLC-UV, MS and nanopore sequencing to verify that Z exists in Acinetobacter phage SH-Ab 15497 and completely replaced adenine. Restriction endonucleases usually cannot digest Z-DNA at recognition sites containing A. Therefore, Z-DNA gives phage an evolutionary advantage to evade attack by host restriction endonucleases. The findings of Z-genome biosynthesis will shed light on the development of new nucleic acid agents and novel DNA technologies.

Key words: phage, Z-genome, Z-base, new nucleic acid agents, biosynthesis

摘要：

Science期刊于2021年4月30日刊登了3篇关于Z-基因组的研究论文。本文将重点评论其中赵素文、张雁和赵惠民三个实验室的合作论文：介绍多酶系统介导的Z-基因组生物合成、降低宿主菌中dATP浓度的dATPase和DUF550发现，并阐明Z-基因组的测序鉴定和功能意义。44年前，苏联科学家首次发现二氨基嘌呤（Z）存在于蓝藻噬菌体（cyanophage）S-2L的基因组中。Z是一种特殊的碱基，它完全取代了腺嘌呤并与胸腺嘧啶形成三个氢键，Z-基因组的生物合成通路一直是未解之谜。上海科技大学赵素文实验室、天津大学张雁实验室和伊利诺伊大学厄巴纳-香槟分校/新加坡科技研究局的赵惠民实验室组成的合作团队，通过生物信息学、计算生物学和生物化学手段揭示了负责Z-基因组生物合成的多酶系统。研究发现此通路可能也存在于数十个分布在全球各地的噬菌体中，包括在上海被发现和分离的Acinetobacter phage SH-Ab 15497。合作团队使用HPLC-UV、质谱技术和纳米孔测序验证了Z碱基存在于Acinetobacter phage SH-Ab 15497中，且完全取代了A碱基，识别位点中含有A碱基的限制性核酸内切酶通常无法切割Z-DNA，因此Z-DNA赋予了噬菌体逃避宿主限制性核酸内切酶攻击的进化优势。Z基因组生物合成通路的解析，可促进新型核酸产品和相关新DNA技术的开发。

关键词: 噬菌体, Z-基因组, Z碱基, 新型核酸, 生物合成