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

Science. 2021 Apr 30;372(6541):516-520. doi: 10.1126/science.abe6494.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / chemistry
  • 2-Aminopurine / metabolism
  • Adenylosuccinate Synthase / chemistry*
  • Adenylosuccinate Synthase / classification
  • Adenylosuccinate Synthase / genetics
  • Bacteriophages / chemistry*
  • Bacteriophages / enzymology*
  • Bacteriophages / genetics
  • Biosynthetic Pathways*
  • Crystallography, X-Ray
  • DNA, Viral / chemistry*
  • DNA, Viral / genetics
  • Genome, Viral
  • Phylogeny
  • Viral Nonstructural Proteins / chemistry*
  • Viral Nonstructural Proteins / classification
  • Viral Nonstructural Proteins / genetics


  • DNA, Viral
  • Viral Nonstructural Proteins
  • 2-Aminopurine
  • 2,6-diaminopurine
  • Adenylosuccinate Synthase