InChI=1S/C10H17N6O12P3/c11-8-7-9(15-10(12)14-8)16(3-13-7)6-1-4(17)5(26-6)2-25-30(21,22)28-31(23,24)27-29(18,19)20/h3-6,17H,1-2H2,(H,21,22)(H,23,24)(H2,18,19,20)(H4,11,12,14,15)/p-4/t4-,5+,6+/m0/s1 |
JFVJZFMWJVSZNC-KVQBGUIXSA-J |
NC1=NC(=NC2=C1N=CN2[C@@H]3O[C@H](COP(=O)(OP(=O)(OP(=O)([O-])[O-])[O-])[O-])[C@@H](O)C3)N |
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Outgoing
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2-amino-2'-deoxyadenosine 5'-triphosphate(4−)
(CHEBI:172931)
is a
2'-deoxyribonucleoside 5'-triphosphate(4−)
(CHEBI:61560)
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Zhou Y, Xu X, Wei Y, Cheng Y, Guo Y, Khudyakov I, Liu F, He P, Song Z, Li Z, Gao Y, Ang EL, Zhao H, Zhang Y, Zhao S (2021) A widespread pathway for substitution of adenine by diaminopurine in phage genomes. Science (New York, N.Y.) 372, 512-516 (Source: SUBMITTER) [PubMed:33926954] [show Abstract] DNA modifications vary in form and function but generally do not alter Watson-Crick base pairing. Diaminopurine (Z) is an exception because it completely replaces adenine and forms three hydrogen bonds with thymine in cyanophage S-2L genomic DNA. However, the biosynthesis, prevalence, and importance of Z genomes remain unexplored. Here, we report a multienzyme system that supports Z-genome synthesis. We identified dozens of globally widespread phages harboring such enzymes, and we further verified the Z genome in one of these phages, Acinetobacter phage SH-Ab 15497, by using liquid chromatography with ultraviolet and mass spectrometry. The Z genome endows phages with evolutionary advantages for evading the attack of host restriction enzymes, and the characterization of its biosynthetic pathway enables Z-DNA production on a large scale for a diverse range of applications. | Sleiman D, Garcia PS, Lagune M, Loc'h J, Haouz A, Taib N, Röthlisberger P, Gribaldo S, Marlière P, Kaminski PA (2021) A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science (New York, N.Y.) 372, 516-520 (Source: SUBMITTER) [PubMed:33926955] [show Abstract] 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. | Pezo V, Jaziri F, Bourguignon PY, Louis D, Jacobs-Sera D, Rozenski J, Pochet S, Herdewijn P, Hatfull GF, Kaminski PA, Marliere P (2021) Noncanonical DNA polymerization by aminoadenine-based siphoviruses. Science (New York, N.Y.) 372, 520-524 (Source: SUBMITTER) [PubMed:33926956] [show Abstract] Bacteriophage genomes harbor the broadest chemical diversity of nucleobases across all life forms. Certain DNA viruses that infect hosts as diverse as cyanobacteria, proteobacteria, and actinobacteria exhibit wholesale substitution of aminoadenine for adenine, thereby forming three hydrogen bonds with thymine and violating Watson-Crick pairing rules. Aminoadenine-encoded DNA polymerases, homologous to the Klenow fragment of bacterial DNA polymerase I that includes 3'-exonuclease but lacks 5'-exonuclease, were found to preferentially select for aminoadenine instead of adenine in deoxynucleoside triphosphate incorporation templated by thymine. Polymerase genes occur in synteny with genes for a biosynthesis enzyme that produces aminoadenine deoxynucleotides in a wide array of Siphoviridae bacteriophages. Congruent phylogenetic clustering of the polymerases and biosynthesis enzymes suggests that aminoadenine has propagated in DNA alongside adenine since archaic stages of evolution. |
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