Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Collaborative Innovation Center of Chemical Science and Engineering, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Frontiers Science Center for Synthetic Biology, Ministry of Education, Tianjin University, Tianjin, China.
Nat Microbiol. 2023 Jul;8(7):1330-1338. doi: 10.1038/s41564-023-01410-1. Epub 2023 Jun 12.
Many bacteriophages evade bacterial immune recognition by substituting adenine with 2,6-diaminopurine (Z) in their genomes. The Z-genome biosynthetic pathway involves PurZ that belongs to the PurA (adenylosuccinate synthetase) family and bears particular similarity to archaeal PurA. However, how the transition of PurA to PurZ occurred during evolution is not clear; recapturing this process may shed light on the origin of Z-containing phages. Here we describe the computer-guided identification and biochemical characterization of a naturally existing PurZ variant, PurZ0, which uses guanosine triphosphate as the phosphate donor rather than the ATP used by PurZ. The atomic resolution structure of PurZ0 reveals a guanine nucleotide binding pocket highly analogous to that of archaeal PurA. Phylogenetic analyses suggest PurZ0 as an intermediate during the evolution of archaeal PurA to phage PurZ. Maintaining the balance of different purines necessitates further evolvement of guanosine triphosphate-using PurZ0 to ATP-using PurZ in adaptation to Z-genome life.
许多噬菌体通过在其基因组中用 2,6-二氨基嘌呤 (Z) 替代腺嘌呤来逃避细菌免疫识别。Z 基因组生物合成途径涉及 PurZ，它属于 PurA（腺嘌呤琥珀酸合成酶）家族，与古菌 PurA 具有特殊的相似性。然而，在进化过程中 PurA 如何转变为 PurZ 尚不清楚；重新捕获这个过程可能有助于揭示含 Z 噬菌体的起源。在这里，我们描述了 PurZ 变体 PurZ0 的计算机指导识别和生化特性，PurZ0 使用鸟苷三磷酸作为磷酸供体，而不是 PurZ 使用的 ATP。PurZ0 的原子分辨率结构揭示了一个高度类似于古菌 PurA 的鸟嘌呤核苷酸结合口袋。系统发育分析表明，PurZ0 是古菌 PurA 向噬菌体 PurZ 进化过程中的一个中间产物。维持不同嘌呤的平衡需要进一步进化使用鸟苷三磷酸的 PurZ0 以适应 Z 基因组生命而使用 ATP 的 PurZ。
