The DNAs of bacterial viruses are known to contain diverse, chemically complex modifications to thymidine that protect them from the endonuclease-based defenses of their cellular hosts, but whose biosynthetic origins are enigmatic. Up to half of thymidines in the Pseudomonas phage M6, the Salmonella phage ViI, and others, contain exotic chemical moieties synthesized through the post-replicative modification of 5-hydroxymethyluridine (5-hmdU). We have determined that these thymidine hypermodifications are derived from free amino acids enzymatically installed on 5-hmdU. These appended amino acids are further sculpted by various enzyme classes such as radical SAM isomerases, PLP-dependent decarboxylases, flavin-dependent lyases and acetyltransferases. The combinatorial permutations of thymidine hypermodification genes found in viral metagenomes from geographically widespread sources suggests an untapped reservoir of chemical diversity in DNA hypermodifications.

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胸苷过度修饰的途径

众所周知，细菌病毒的 DNA 含有对胸苷的多种化学复杂修饰，可保护它们免受细胞宿主基于核酸内切酶的防御，但其生物合成起源是神秘的。假单胞菌噬菌体 M6、沙门氏菌噬菌体 ViI 等中多达一半的胸苷含有通过 5-羟甲基尿苷 (5-hmdU) 的复制后修饰合成的外来化学部分。我们已经确定这些胸苷超修饰来源于酶促安装在 5-hmdU 上的游离氨基酸。这些附加的氨基酸由各种酶类进一步雕刻，例如自由基 SAM 异构酶、PLP 依赖性脱羧酶、黄素依赖性裂合酶和乙酰转移酶。