Journal
SCIENCE
Volume 372, Issue 6541, Pages 516-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abe6494
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Funding
- ERASynBio TNA episome
- ERACoBioTech Iron Plug'n Play fellowship
- French National Agency [ANR-16-CE02-0005-01]
- French government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases [ANR-10-LABX-62-IBEID]
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This study reveals a third purine pathway encoded by cyanobacterial virus S-2L and Vibrio phage PhiVC8, catalyzed by PurZ, which synthesizes 2-amino-2'-deoxyadenosine-5'-triphosphate. Crystallography and phylogenetics analyses show a close relationship between phage PurZ and archaeal PurA enzymes. This work elucidates a biocatalytic innovation beyond canonical molecular biology, remodeling a DNA building block.
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.
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