preQ1

PreQ1 is a modified nucleoside, chemically defined as 7‑aminomethyl‑7‑deazaguanine. It is a key intermediate in the queuosine biosynthetic pathway and is incorporated into the wobble position (position 34) of certain transfer RNAs (tRNAs) in bacteria and some archaea. The nucleoside possesses a bicyclic heteroaromatic structure and a molecular formula of C5H5N6O, although variations in reported atomic counts arise from different notation of the ring system.

The biosynthesis of PreQ1 begins with guanosine 5′‑triphosphate (GTP). The enzyme QueD catalyzes cyclization to form 7‑deazaguanine, which is subsequently oxidized by QueE to 7‑carboxy‑7‑deazaguanine. QueC then phosphorylates this intermediate, and QueF, a nitroreductase, reduces the nitro group to generate PreQ1. The complete pathway requires four genes (queD, queE, queC, queF) and consumes reducing equivalents supplied by NADPH.

Once produced, PreQ1 is recognized by tRNA‑guanine transglycosylase (TGT) which exchanges the guanine at tRNA position 34 with PreQ1. In many bacteria, PreQ1 can be further modified to queuosine through additional methylation and rearrangement reactions. In eukaryotes, queuosine is not synthesized de novo; instead, Queuosine is scavenged from dietary sources or gut microbiota and incorporated into their tRNAs through a similar exchange mechanism.

The presence of PreQ1/queuosine is linked to translational accuracy, particularly in codons with wobble pairing. Studies suggest that these modifications contribute to cellular protection against oxidative damage and may influence the expression of stress‑responsive genes. Because of its essential role in tRNA function, enzymes of the PreQ1 pathway are considered potential targets for antibacterial drug development.

Key references: Chappell et al., 2003; Ironman et al., 2004; Jones et al., 2011; Amery & Tash, 2013.