A widespread pathway for substitution of adenine by diaminopurine in phage genomes
Authors: Yan Zhou
Yan Zhang
Zhangyue Song
Huimin Zhao
Ping He
Zhi Li
Yu Cheng
Yan Gao
Suwen Zhao
Ivan Khudyakov
Ee Lui Ang
Xuexia Xu
Fuli Liu
Yu Guo
Yifeng Wei
Journal: Science (2021)
Discipline: Multidisciplinary
Keywords: DNA modifications; diaminopurine; Z genome; cyanophage S-2L; multienzyme system
Affiliations: Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China., Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300072, China., iHuman Institute, ShanghaiTech University, Shanghai 201210, China., School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., University of Chinese Academy of Sciences, Beijing 100049, China., Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai 200061, China., Singapore Institute of Food and Biotechnology Innovation, Agency for Science, Technology and Research (A*STAR), Singapore., All-Russian Research Institute for Agricultural Microbiology, St. Petersburg 196608, Russia., Department of Medical Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Biomedical Big Data Platform, SIAIS, ShanghaiTech University, Shanghai 201210, China., Singapore Institute of Food and Biotechnology Innovation, Agency for Science, Technology and Research (A*STAR), Singapore.   ., Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA., Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.   ., iHuman Institute, ShanghaiTech University, Shanghai 201210, China.   .

Abstract:  DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importance of Z genomes remain unexplored. Here, we report a multienzyme system that supports Z-genome synthesis. We identified dozens of globally widespread phages harboring such enzymes, and we further verified the Z genome in one of these phages, Acinetobacter phage SH-Ab 15497, by using liquid chromatography with ultraviolet and mass spectrometry. The Z genome endows phages with evolutionary advantages for evading the attack of host restriction enzymes, and the characterization of its biosynthetic pathway enables Z-DNA production on a large scale for a diverse range of applications. 

Retracted: No

PubPeer comments:
 The article describes the complete replacement of adenosine (A) by diaminopurine (Z) in the genome of cyanophage S-2L, back-to-back with two further publications on the same topic. The analyses in these publications nicely clarify the biochemistry behind this old observation [1] and show that this alternative form of DNA is widespread in phages. Nicely, one of the co-authors of the original description of this phenomenon [1] appears to be a co-author on the current publication. The authors choose to call this DNA Z-DNA. However, the name Z-DNA already exists. It is taught in Genetics 101 classes as one of the major conformations of DNA double helices. Specifically, it is a left-handed form. Z-DNA is formed in vivo and Z-DNA formation at local DNA sites is thought to act as a regulatory switch. A simple google search for the term quickly reveals recent and not so recent reviews on the topic, eg. refs. [2], [3],[4]. Consequently, Z-DNA has a quite detailed entry at wikipedia, https: en.wikipedia.org wiki Z-DNA. It is a bit unclear to me, why authors and editors have chosen to still use this term. A perspective in the same issue of Science chooses instead the term dZ-DNA [5]. However, a news feature in Nature [6] adopts the terminology. This is bound to cause confusion and it would be nice if authors and or editors could clarify why they think it appropriate to appropriate the name Z-DNA for their unrelated finding. * [1] https: doi.org 10.1038 270369a0 * [2] https: doi.org 10.2741 2399 * [3] https: dx.doi.org 10.1007%2Fs12551-019-00534-1 * [4] https: doi.org 10.1038 s42003-018-0237-x * [5] https: doi.org 10.1126 science.abh3571 * [6] https: www.nature.com articles d41586-021-01157-x ,