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Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens.


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.

SUBMITTER: Yuan Y 

PROVIDER: S-EPMC6754566 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens.

Yuan Yifeng Y   Zallot Rémi R   Grove Tyler L TL   Payan Daniel J DJ   Martin-Verstraete Isabelle I   Šepić Sara S   Balamkundu Seetharamsingh S   Neelakandan Ramesh R   Gadi Vinod K VK   Liu Chuan-Fa CF   Swairjo Manal A MA   Dedon Peter C PC   Almo Steven C SC   Gerlt John A JA   de Crécy-Lagard Valérie V  

Proceedings of the National Academy of Sciences of the United States of America 20190903 38


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 preQ<sub>0</sub> and preQ<sub>1</sub> also occurs. With the exception of <i>Escherichia coli</i> YhhQ, shown to transport preQ<sub>0</sub> and preQ  ...[more]

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