Archaea's Unique Modifier♦

♦ See referenced article, J. Biol. Chem. 2010, 285, 12706–12713

One of the unique molecular features of Archaea is the presence of a modified nucleoside known as archaeosine (7-deazaguanosine, or G⁺) at the 15-position of most tRNAs. This modification is believed to help stabilize tRNA structure through ionic interactions, which is critical as many Archaea are thermophiles. Although some elements of the archaeosine biosynthetic pathway are known, the final step(s) involving the conversion of cyano-7-deazaguanine (preQ₀) to G⁺ have remained elusive, until now. In this Paper of the Week, Gabriela Phillips and colleagues employed an elegant comparative and functional genomics approach to identify the enzyme responsible for this last part. The candidate protein is a paralog of tRNA-guanine transglycosylase (arcTGT), the enzyme that inserts preQ₀ into the tRNA, and is thus known as TgtA2. To confirm this candidate, Phillips and colleagues constructed a ΔtgtA2 mutant of Haloferax volcanii and demonstrated that this strain lacks G⁺ in tRNA and accumulates preQ₀. They next purified TgtA2 from another archaeal species (Methanocaldococcus jannaschii) and found that this enzyme performs a previously unidentified chemistry, the conversion of a nitrile to formamidine. This work provides an important contribution to the study of microbial metabolism and also offers a fine example on how to exploit sequenced genomes to identify enzymes involved in biochemical pathways.

The final portion of archaeosine biosynthesis, including the predicted role of TgtA2 as demonstrated in this study.