Cells have two purine pathways that synthesize adenine and guanine ribonucleotides from phosphoribose via inosylate. A chemical hybrid between adenine and guanine, 2-aminoadenine (Z), replaces adenine in the DNA of the cyanobacterial virus S-2L. We show that S-2L and Vibrio phage PhiVC8 encode a third purine pathway catalyzed by PurZ, a distant paralog of succinoadenylate synthase (PurA), the enzyme condensing aspartate and inosylate in the adenine pathway. PurZ condenses aspartate with deoxyguanylate into dSMP (N6-succino-2-amino-2′-deoxyadenylate), which undergoes defumarylation and phosphorylation to give dZTP (2-amino-2′-deoxyadenosine-5′-triphosphate), a substrate for the phage DNA polymerase. Crystallography and phylogenetics analyses indicate a close relationship between phage PurZ and archaeal PurA enzymes. Our work elucidates the biocatalytic innovation that remodeled a DNA building block beyond canonical molecular biology.

细胞具有两个嘌呤途径，通过肌苷从磷酸核糖合成腺嘌呤和鸟嘌呤核糖核苷酸。腺嘌呤和鸟嘌呤之间的化学混合物2-氨基腺嘌呤（Z）取代了蓝细菌病毒S-2L DNA中的腺嘌呤。我们展示了S-2L和弧菌噬菌体PhiVC8编码由PurZ催化的第三条嘌呤途径，这是一种遥远的琥珀酰腺苷酸合酶（PurA）旁系同源物，该酶在腺嘌呤途径中浓缩天冬氨酸和肌醇。PurZ将天冬氨酸与脱氧鸟苷酸缩合成dSMP（N6-琥珀酰-2-氨基-2'-脱氧腺苷酸），然后进行脱迷迭香和磷酸化反应，生成dZTP（2-氨基-2'-脱氧腺苷-5'-三磷酸酯）。噬菌体DNA聚合酶。晶体学和系统发育分析表明噬菌体PurZ和古细菌PurA酶之间的密切关系。我们的工作阐明了生物催化创新，该创新重塑了超越常规分子生物学的DNA构建基块。