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.

DNA修饰的形式和功能各不相同，但通常不会改变Watson-Crick碱基配对。二氨基嘌呤（Z）是一个例外，因为它可以完全取代腺嘌呤，并在蓝藻S-2L基因组DNA中与胸腺嘧啶形成三个氢键。但是，Z基因组的生物合成，普遍性和重要性仍待探索。在这里，我们报告了一种支持Z基因组合成的多酶系统。我们鉴定了数十种带有这种酶的全球噬菌体，并进一步验证了其中一种噬菌体不动杆菌的Z基因组噬菌体SH-Ab 15497，通过使用具有紫外和质谱的液相色谱法。Z基因组赋予噬菌体逃避宿主限制性内切酶攻击的进化优势，其生物合成途径的表征使Z-DNA大规模生产，可用于多种应用。