关键词: 噬菌体, Z-基因组, Z碱基, 新型核酸, 生物合成

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