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Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens
Edited by Tina M. Henkin, The Ohio State University, Columbus, OH, and approved August 1, 2019 (received for review June 16, 2019)

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Significance
Queuosine (Q) is a tRNA modification found in eukaryotes and bacteria that plays an important role in translational efficiency and accuracy. Queuine (q), the Q nucleobase, is increasingly appreciated as an important micronutrient that contributes to human health. We describe here that q salvage pathways exist in bacteria, including many pathogens and host-associated organisms, suggesting a direct competition for the q precursor in the human gut microbiome. We also show how a rational use of comparative genomics can lead to the discovery of novel types of enzymatic reactions, illustrated by the discovery of the queuine lyase enzyme.
Abstract
Queuosine (Q) is a complex tRNA modification widespread in eukaryotes and bacteria that contributes to the efficiency and accuracy of protein synthesis. Eukaryotes are not capable of Q synthesis and rely on salvage of the queuine base (q) as a Q precursor. While many bacteria are capable of Q de novo synthesis, salvage of the prokaryotic Q precursors preQ0 and preQ1 also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ0 and preQ1, the enzymes and transporters involved in Q salvage and recycling have not been well described. We discovered and characterized 2 Q salvage pathways present in many pathogenic and commensal bacteria. The first, found in the intracellular pathogen Chlamydia trachomatis, uses YhhQ and tRNA guanine transglycosylase (TGT) homologs that have changed substrate specificities to directly salvage q, mimicking the eukaryotic pathway. The second, found in bacteria from the gut flora such as Clostridioides difficile, salvages preQ1 from q through an unprecedented reaction catalyzed by a newly defined subgroup of the radical-SAM enzyme family. The source of q can be external through transport by members of the energy-coupling factor (ECF) family or internal through hydrolysis of Q by a dedicated nucleosidase. This work reinforces the concept that hosts and members of their associated microbiota compete for the salvage of Q precursors micronutrients.
Footnotes
↵1Y.Y., R.Z., and T.L.G. contributed equally to this work.
- ↵2To whom correspondence may be addressed. Email: vcrecy{at}ufl.edu.
Author contributions: Y.Y., R.Z., I.M.-V., S.C.A., J.A.G., and V.d.C.-L. designed research; Y.Y., R.Z., T.L.G., D.J.P., and I.M.-V. performed research; S.B., R.N., V.K.G., C.-F.L., and P.C.D. contributed new reagents/analytic tools; Y.Y., R.Z., T.L.G., S.Š., M.A.S., and V.d.C.-L. analyzed data; and Y.Y., R.Z., T.L.G., I.M.-V., P.C.D., and V.d.C.-L. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Protein Data Bank, https://www.rcsb.org (ID code 6P78).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1909604116/-/DCSupplemental.
Published under the PNAS license.
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