Pathways of thymidine hypermodification.

Pathways of thymidine hypermodification.
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DOI:
10.1093/nar/gkab781
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发表时间:
2022-04-08
影响因子:
14.9
通讯作者:
Weigele PR
Weigele PR
中科院分区:
生物学2区
文献类型:
--
作者:
Lee YJ;Dai N;Müller SI;Guan C;Parker MJ;Fraser ME;Walsh SE;Sridar J;Mulholland A;Nayak K;Sun Z;Lin YC;Comb DG;Marks K;Gonzalez R;Dowling DP;Bandarian V;Saleh L;Corrêa IR;Weigele PR

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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. Pathways of thymidine hypermodification.
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