preQ0

PreQ0 is the abbreviation for 7‑cyano‑7‑deazaguanine, a modified nucleobase that serves as an intermediate in the queuosine biosynthetic pathway found in many bacteria, archaea, and eukaryotic mitochondria. Chemically, PreQ0 is a purine analog in which the C‑7 position of the guanine ring contains a cyano substituent and the C‑2 nitrogens are replaced by a carbon atom, producing a “deaza” structure. This modification alters the electronic properties of the base and is recognized by specialized enzymes that convert it into the final queuosine nucleoside.

The formation of PreQ0 begins with the deamination of guanosine 7‑phosphate, followed by a series of reactions involving the enzymes QueD, QueE, and QueF that introduce the cyano group and establish the deaza ring. The pathway is highly conserved among prokaryotes but is absent in many eukaryotes, which instead use a different route to synthesize queuosine in the cytoplasm and transfer it to tRNA via a post‑transcriptional modification step.

PreQ0 is incorporated into tRNA molecules, replacing guanine at the wobble position (position 34) of tRNAs that encode asparagine, aspartic acid, histidine, and tyrosine. The resulting queuosine heterocycle enhances the accuracy and efficiency of translation by improving codon‑anticodon pairing and protecting the tRNA against oxidative damage. In bacteria, disruption of PreQ0 synthesis can lead to growth defects and increased susceptibility to antibiotics, underscoring its physiological importance.

Because PreQ0 is an essential precursor for queuosine biosynthesis, it has become a target for antimicrobial drug development. Small‑molecule inhibitors that block the Que enzymes effectively halt PreQ0 production, leading to impaired tRNA modification and reduced bacterial viability. Ongoing research continues to map the structural details of PreQ0‑binding enzymes and to evaluate the therapeutic potential of targeting this pathway.