Enzymatic Synthesis of the Unnatural Nucleotide 2’-Deoxyisoguanosine 5’-Monophosphate

Fuping Zhao, Yifeng Wei, Xinyu Wang, Yan Zhou, Yang Tong, Ee Lui Ang, Shengnan Liu, Huimin Zhao, Yan Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Naturally occurring DNA contains four canonical bases, forming two Watson-Crick base pairs (adenine-thymine, guanine-cytosine). Efforts over the past decades have led to the development of several unnatural base pairs, enabling the synthesis of unnatural DNA with an expanded genetic alphabet. The engineering of organisms capable of de novo biosynthesis of unnatural DNA would have significant technological and philosophical implications, but remains a challenge. Here we report the enzymatic conversion of 2’-deoxyxanthosine 5’-monophosphate (dXMP) into deoxyisoguanosine monophosphate (dBMP), a precursor of the unnatural isoguanine-isocytosine base pair. The reaction is catalyzed by the bacteriophage enzyme PurZ and bacterial PurB, and is a key addition to the toolbox for de novo biosynthesis of unnatural DNA.

Original languageEnglish (US)
Article numbere202200295
JournalChemBioChem
Volume23
Issue number21
Early online dateSep 22 2022
DOIs
StatePublished - Nov 4 2022

Keywords

  • DNA
  • adenylosuccinate synthetases
  • bacteriophages
  • isoguanine
  • unnatural base pairs

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Organic Chemistry

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