There are abundant base modifications in bacteriophages' genomes, mainly for avoiding the digestion of host endonucleases. More than 40 years ago, researchers discovered that 2-amino-adenine (Z) completely replaced adenine (A) and forms a complementary pairing with three hydrogen bonds with thymine (T) in the DNA of cyanophage S-2L, forming a distinct "Z-genome". In recent years, researchers have discovered and validated the biosynthetic pathway of Z-genome in various bacteriophages, constituting a multi-enzyme system. This system includes the phage-encoded enzymes deoxy-2'-aminoadenylosuccinate synthetase (PurZ), deoxyadenosine triphosphate hydrolase (dATPase/DatZ), deoxyadenosine/deoxyguanosine triphosphate pyrophosphatase (DUF550/MazZ) and DNA polymerase (DpoZ). In this review, we provide a concise overview of the historical discovery on diversely modified nucleosides in bacteriophages, then we comprehensively summarize the research progress on multiple enzymes involved in the Z-genome biosynthetic pathway. Finally, the potential applications of the Z-genome and the enzymes in its biosynthetic pathway are discussed in order to provide reference for research in this field.
噬菌体基因组中存在丰富的碱基修饰，主要用于逃避宿主内切酶的切割。40多年前，在蓝藻噬菌体S-2L的DNA中，研究者发现2-氨基腺嘌呤(Z)完全取代腺嘌呤(A)，与胸腺嘧啶(T)形成具有三根氢键的互补配对，形成了特殊的Z基因组。近年来，研究者在多个噬菌体中发现并证实了噬菌体Z基因组生物合成通路。该通路是一个多酶系统，其中包含由噬菌体DNA编码的2-氨基脱氧腺苷琥珀酸合成酶(PurZ)、脱氧腺苷三磷酸水解酶(dATPase/DatZ)、脱氧腺苷/脱氧鸟苷三磷酸的焦磷酸水解酶(DUF550/MazZ)和DNA聚合酶(DpoZ)。本文在简述噬菌体中各种修饰核苷发现历史的基础上，详细介绍了Z基因组生物合成通路中多种酶的研究进展，最后对Z基因组及其合成通路中多种酶的应用进行了展望，以期为该领域的研究提供借鉴和参考。.
Keywords: 2-aminoadenine; DNA modification; Z-genome; bacteriophage; biosynthetic pathway.