TET/JBP (ten-eleven translocation/base J binding protein) enzymes are iron(II)- and 2-oxo-glutarate–dependent dioxygenases that are found in all kingdoms of life and oxidize 5-methylpyrimidines on the polynucleotide level. Despite their prevalence, few examples have been biochemically characterized. Among those studied are the metazoan TET enzymes that oxidize 5-methylcytosine in DNA to hydroxy, formyl, and carboxy forms and the euglenozoa JBP dioxygenases that oxidize thymine in the first step of base J biosynthesis. Both enzymes have roles in epigenetic regulation. It has been hypothesized that all TET/JBPs have their ancestral origins in bacteriophages, but only eukaryotic orthologs have been described. Here we demonstrate the 5mC-dioxygenase activity of several phage TETs encoded within viral metagenomes. The clustering of these TETs in a phylogenetic tree correlates with the sequence specificity of their genomically cooccurring cytosine C5-methyltransferases, which install the methyl groups upon which TETs operate. The phage TETs favor Gp5mC dinucleotides over the 5mCpG sites targeted by the eukaryotic TETs and are found within gene clusters specifying complex cytosine modifications that may be important for DNA packaging and evasion of host restriction.

TET/JBP（10-11 易位/碱基 J 结合蛋白）酶是铁 (II) 和 2-氧代戊二酸依赖性双加氧酶，存在于所有生命王国中，并在多核苷酸水平上氧化 5-甲基嘧啶。尽管它们很普遍，但很少有例子被生化表征。其中研究的是后生动物 TET 酶，将 DNA 中的 5-甲基胞嘧啶氧化成羟基、甲酰基和羧基形式，以及在碱基 J 生物合成的第一步中氧化胸腺嘧啶的裸眼动物 JBP 双加氧酶。两种酶都在表观遗传调控中起作用。已经假设所有 TET/JBP 的祖先起源于噬菌体，但只描述了真核直向同源物。在这里，我们展示了病毒宏基因组中编码的几种噬菌体 TET 的 5mC-双加氧酶活性。这些 TET 在系统发育树中的聚类与它们在基因组上同时发生的胞嘧啶 C5-甲基转移酶的序列特异性相关，胞嘧啶 C5-甲基转移酶安装了 TET 在其上运行的甲基。噬菌体 TET 比真核 TET 靶向的 5mCpG 位点更偏向 Gp5mC 二核苷酸，并且在指定复杂胞嘧啶修饰的基因簇中发现，这可能对 DNA 包装和逃避宿主限制很重要。