A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes

Dona Sleiman; Pierre Simon Garcia; Marion Lagune; Jerome Loc'H; Ahmed Haouz; Najwa Taib; Pascal Röthlisberger; Simonetta Gribaldo; Philippe Marlière; Pierre-Alexandre Kaminski

doi:10.1126/science.abe6494

Journal articles

A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes

Dona Sleiman ¹ Pierre Simon Garcia ^{2, 3} Marion Lagune ¹ Jerome Loc'H ⁴ Ahmed Haouz ⁵ Najwa Taib ^{2, 6} Pascal Röthlisberger ⁷ Simonetta Gribaldo ² Philippe Marlière ⁸ Pierre-Alexandre Kaminski ^{1, *}

* Corresponding author

1 Biologie des Bactéries pathogènes à Gram-positif

2 Biologie Evolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell

3 SAMe - Adaptation au stress et Métabolisme chez les entérobactéries - Stress adaptation and metabolism in enterobacteria

4 Dynamique structurale des Macromolécules / Structural Dynamics of Macromolecules

5 Cristallographie (Plate-forme)

6 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

7 Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids

8 UMR 8030 - Génomique métabolique

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Biochemistry, Molecular Biology / Biomolecules [q-bio.BM]

Life Sciences [q-bio] / Biochemistry, Molecular Biology / Biomolecules [q-bio.BM]

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https://hal-pasteur.archives-ouvertes.fr/pasteur-03228896
Contributor : Pierre Alexandre Kaminski <>
Submitted on : Tuesday, May 18, 2021 - 2:47:14 PM
Last modification on : Thursday, July 1, 2021 - 11:04:04 AM

A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes

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A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes

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