Four additional natural 7-deazaguanine derivatives in phages and how to make them.

Four additional natural 7-deazaguanine derivatives in phages and how to make them.
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DOI:
10.1093/nar/gkad657
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发表时间:
2023-09-22
影响因子:
14.9
通讯作者:
--
中科院分区:
生物学2区
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噬菌体和细菌在进行一场持续的军备竞赛,不断进化出新的分子工具来相互生存。为了保护它们的基因组DNA免受限制性内切酶(最常见的细菌防御系统)的侵害,双链DNA噬菌体进化出了影响所有四种碱基的复杂修饰。本研究的重点是鸟嘌呤第7位的修饰。共鉴定出8个7-去氮鸟嘌呤衍生物,包括4个未知衍生物:2 ' -脱氧-7-(甲氨基)甲基-7-去氮鸟嘌呤(mdPreQ1)、2 ' -脱氧-7-(甲氨基)甲基-7-去氮鸟嘌呤(fdPreQ1)、2 ' -脱氧-7-去氮鸟嘌呤(dDG)和2 ' -脱氧-7-羧基-7-去氮鸟嘧啶(dCDG)。这些修饰通过一种名为DpdA的鸟嘌呤转糖基化酶插入DNA。DpdA的三个亚家族先前已被表征:bDpdA, DpdA1和DpdA2。在这项工作中确定了另外两个亚家族:允许完全替代鸟嘌呤的DpdA3和对古细菌病毒特异性的DpdA4。现在已经在所有携带7-去氮杂鸟嘌呤修饰的噬菌体和病毒中发现了转糖基酶,这表明这些修饰的插入是复制后事件。预计有三种酶参与了这些新发现的DNA修饰的生物合成:7-羧基-7-脱氮鸟嘌呤脱羧酶(DpdL)、dPreQ1甲酰转移酶(DpdN)和dPreQ1甲基转移酶(DpdM),这些酶经过实验验证,具有以前未观察到的核酸甲基化酶的独特折叠。
Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2′-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ1), 2′-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ1), 2′-deoxy-7-deazaguanine (dDG) and 2′-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ1 formyltransferase (DpdN) and dPreQ1 methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.
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