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Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19126-19135. doi: 10.1073/pnas.1909604116. Epub 2019 Sep 3.

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

Author information

1
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611.
2
Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
3
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461.
4
Laboratoire de Pathogénèse des Bactéries Anaérobies, Institut Pasteur et Université de Paris, F-75015 Paris, France.
5
Singapore-MIT Alliance for Research and Technology, Infectious Disease Interdisciplinary Research Group, 138602 Singapore, Singapore.
6
Department of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182.
7
The Viral Information Institute, San Diego State University, San Diego, CA 92182.
8
Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.
9
Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
10
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
11
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
12
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611; vcrecy@ufl.edu.
13
University of Florida Genetics Institute, Gainesville, FL 32610.

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.

KEYWORDS:

comparative genomics; nucleoside transport; queuosine; rSAM; sequence similarity network

PMID:
31481610
PMCID:
PMC6754566
[Available on 2020-03-03]
DOI:
10.1073/pnas.1909604116

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