DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: 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 preQ0and preQ1also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ0and preQ1, the enzymes and transporters involved in Q salvage and recycling have not been well described. In this work, 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 preQ1from 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 thatmore » hosts and members of their associated microbiota compete for the salvage of Q precursors micronutrients.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [1];  [5];  [5];  [5];  [5];  [6];  [7];  [3];  [2];  [1]
  1. Univ. of Florida, Gainesville, FL (United States)
  2. Univ. of Illinois at Urbana-Champaign, IL (United States)
  3. Albert Einstein College of Medicine, Bronx, NY (United States)
  4. Inst. Pasteur, Paris (France); Univ. de Paris (France)
  5. Singapore-MIT Alliance for Research and Technology (Singapore). Infectious Disease Interdisciplinary Research Group
  6. San Diego State Univ., CA (United States)
  7. Singapore-MIT Alliance for Research and Technology (Singapore). Infectious Disease Interdisciplinary Research Group; Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); Price Family Foundation; California Metabolic Research Foundation; USDOE Office of Science (SC); Eli Lilly Company
OSTI Identifier:
1576001
Grant/Contract Number:  
R01 GM70641; P01 GM118303; U54-GM093342; R21-AI133329; U54-GM094662; GM110588; S10 OD020068; AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 38; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; queuosine; nucleoside transport; sequence similarity network; comparative genomics; rSAM

Citation Formats

Yuan, Yifeng, Zallot, Rémi, Grove, Tyler L., Payan, Daniel J., Martin-Verstraete, Isabelle, Šepić, Sara, Balamkundu, Seetharamsingh, Neelakandan, Ramesh, Gadi, Vinod K., Liu, Chuan-Fa, Swairjo, Manal A., Dedon, Peter C., Almo, Steven C., Gerlt, John A., and de Crécy-Lagard, Valérie. Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens. United States: N. p., 2019. Web. doi:10.1073/pnas.1909604116.
Yuan, Yifeng, Zallot, Rémi, Grove, Tyler L., Payan, Daniel J., Martin-Verstraete, Isabelle, Šepić, Sara, Balamkundu, Seetharamsingh, Neelakandan, Ramesh, Gadi, Vinod K., Liu, Chuan-Fa, Swairjo, Manal A., Dedon, Peter C., Almo, Steven C., Gerlt, John A., & de Crécy-Lagard, Valérie. Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens. United States. https://doi.org/10.1073/pnas.1909604116
Yuan, Yifeng, Zallot, Rémi, Grove, Tyler L., Payan, Daniel J., Martin-Verstraete, Isabelle, Šepić, Sara, Balamkundu, Seetharamsingh, Neelakandan, Ramesh, Gadi, Vinod K., Liu, Chuan-Fa, Swairjo, Manal A., Dedon, Peter C., Almo, Steven C., Gerlt, John A., and de Crécy-Lagard, Valérie. Tue . "Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens". United States. https://doi.org/10.1073/pnas.1909604116. https://www.osti.gov/servlets/purl/1576001.
@article{osti_1576001,
title = {Discovery of novel bacterial queuine salvage enzymes and pathways in human pathogens},
author = {Yuan, Yifeng and Zallot, Rémi and Grove, Tyler L. and Payan, Daniel J. and Martin-Verstraete, Isabelle and Šepić, Sara and Balamkundu, Seetharamsingh and Neelakandan, Ramesh and Gadi, Vinod K. and Liu, Chuan-Fa and Swairjo, Manal A. and Dedon, Peter C. and Almo, Steven C. and Gerlt, John A. and de Crécy-Lagard, Valérie},
abstractNote = {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 preQ0and preQ1also occurs. With the exception of Escherichia coli YhhQ, shown to transport preQ0and preQ1, the enzymes and transporters involved in Q salvage and recycling have not been well described. In this work, 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 preQ1from 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.},
doi = {10.1073/pnas.1909604116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 38,
volume = 116,
place = {United States},
year = {Tue Sep 03 00:00:00 EDT 2019},
month = {Tue Sep 03 00:00:00 EDT 2019}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 26 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks
journal, August 2015

  • Gerlt, John A.; Bouvier, Jason T.; Davidson, Daniel B.
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1854, Issue 8
  • DOI: 10.1016/j.bbapap.2015.04.015

Nutrition and Bipartite Metabolism of Intracellular Pathogens
journal, June 2019


Synthesis of the Transfer-RNA Nucleoside Queuosine by Using a Chiral Allyl Azide Intermediate.
journal, July 2007

  • Klepper, Florian; Jahn, Eva-Maria; Hickmann, Volker
  • ChemInform, Vol. 38, Issue 27
  • DOI: 10.1002/chin.200727173

Dali server update
journal, April 2016

  • Holm, Liisa; Laakso, Laura M.
  • Nucleic Acids Research, Vol. 44, Issue W1
  • DOI: 10.1093/nar/gkw357

Slight sequence variations of a common fold explain the substrate specificities of tRNA-guanine transglycosylases from the three kingdoms
journal, October 1997


Transcriptional response of Clostridium difficile to low iron conditions
journal, January 2018

  • Hastie, Jessica L.; Hanna, Phillip C.; Carlson, Paul E.
  • Pathogens and Disease, Vol. 76, Issue 2
  • DOI: 10.1093/femspd/fty009

Increased Expression of Queuosine Synthesizing Enzyme, tRNA-Guanine Transglycosylase, and Queuosine Levels in tRNA of Leukemic Cells
journal, January 2001


Database resources of the National Center for Biotechnology Information
journal, November 2018

  • Sayers, Eric W.; Agarwala, Richa; Bolton, Evan E.
  • Nucleic Acids Research, Vol. 47, Issue D1
  • DOI: 10.1093/nar/gky1069

Structural Insights into Thioether Bond Formation in the Biosynthesis of Sactipeptides
journal, August 2017

  • Grove, Tyler L.; Himes, Paul M.; Hwang, Sungwon
  • Journal of the American Chemical Society, Vol. 139, Issue 34
  • DOI: 10.1021/jacs.7b01283

Reannotation of the genome sequence of Clostridium difficile strain 630
journal, February 2011

  • Monot, M.; Boursaux-Eude, C.; Thibonnier, M.
  • Journal of Medical Microbiology, Vol. 60, Issue 8
  • DOI: 10.1099/jmm.0.030452-0

Basic Local Alignment Search Tool
journal, October 1990


Worlds within worlds: evolution of the vertebrate gut microbiota
journal, October 2008

  • Ley, Ruth E.; Lozupone, Catherine A.; Hamady, Micah
  • Nature Reviews Microbiology, Vol. 6, Issue 10
  • DOI: 10.1038/nrmicro1978

Improvements to PATRIC, the all-bacterial Bioinformatics Database and Analysis Resource Center
journal, November 2016

  • Wattam, Alice R.; Davis, James J.; Assaf, Rida
  • Nucleic Acids Research, Vol. 45, Issue D1
  • DOI: 10.1093/nar/gkw1017

Novel genomic island modifies DNA with 7-deazaguanine derivatives
journal, February 2016

  • Thiaville, Jennifer J.; Kellner, Stefanie M.; Yuan, Yifeng
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 11
  • DOI: 10.1073/pnas.1518570113

Queuosine modification in tRNA and expression of the nitrate reductase in Escherichia coli.
journal, July 1984


Deazaguanine derivatives, examples of crosstalk between RNA and DNA modification pathways
journal, December 2016


Catalysis by nucleoside hydrolases
journal, December 2003


The Queuine Micronutrient: Charting a Course from Microbe to Man
journal, April 2015

  • Fergus, Claire; Barnes, Dominic; Alqasem, Mashael
  • Nutrients, Vol. 7, Issue 4
  • DOI: 10.3390/nu7042897

Prolonging healthy aging: Longevity vitamins and proteins
journal, October 2018


Three-dimensional structure of hyper-modified nucleoside Q located in the wobbling position of tRNA
journal, November 1979

  • Yokoyama, Shigeyuki; Miyazawa, Tatsuo; Iitaka, Yoichi
  • Nature, Vol. 282, Issue 5734
  • DOI: 10.1038/282107a0

Queuosine‐modified tRNAs confer nutritional control of protein translation
journal, August 2018

  • Tuorto, Francesca; Legrand, Carine; Cirzi, Cansu
  • The EMBO Journal, Vol. 37, Issue 18
  • DOI: 10.15252/embj.201899777

Queuine, a modified base incorporated posttranscriptionally into eukaryotic transfer RNA: wide distribution in nature
journal, April 1982


Involvement of protein kinase C in the control of tRNA modification with queuine in HeLa cells
journal, January 1995


Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria
journal, January 2013


A Nutrient-Driven tRNA Modification Alters Translational Fidelity and Genome-wide Protein Coding across an Animal Genus
journal, December 2014


Characterization of the human tRNA-guanine transglycosylase: Confirmation of the heterodimeric subunit structure
journal, March 2010


The Escherichia coli COG1738 Member YhhQ Is Involved in 7-Cyanodeazaguanine (preQ0) Transport
journal, February 2017

  • Zallot, Rémi; Yuan, Yifeng; de Crécy-Lagard, Valérie
  • Biomolecules, Vol. 7, Issue 4
  • DOI: 10.3390/biom7010012

Interactions Between the Gastrointestinal Microbiome and Clostridium difficile
journal, October 2015


Paramagnetic Intermediates Generated by Radical S-Adenosylmethionine (SAM) Enzymes
journal, July 2014

  • Stich, Troy A.; Myers, William K.; Britt, R. David
  • Accounts of Chemical Research, Vol. 47, Issue 8
  • DOI: 10.1021/ar400235n

Identification of the minimal bacterial 2′-deoxy-7-amido-7-deazaguanine synthesis machinery
journal, October 2018

  • Yuan, Yifeng; Hutinet, Geoffrey; Valera, Jacqueline Gamboa
  • Molecular Microbiology, Vol. 110, Issue 3
  • DOI: 10.1111/mmi.14113

Complex Biotransformations Catalyzed by Radical S -Adenosylmethionine Enzymes
journal, July 2011


RegPrecise 3.0 – A resource for genome-scale exploration of transcriptional regulation in bacteria
journal, January 2013

  • Novichkov, Pavel S.; Kazakov, Alexey E.; Ravcheev, Dmitry A.
  • BMC Genomics, Vol. 14, Issue 1
  • DOI: 10.1186/1471-2164-14-745

Structural basis for glycyl radical formation by pyruvate formate-lyase activating enzyme
journal, October 2008

  • Vey, J. L.; Yang, J.; Li, M.
  • Proceedings of the National Academy of Sciences, Vol. 105, Issue 42
  • DOI: 10.1073/pnas.0806640105

Metabolic adaptation of human pathogenic and related nonpathogenic bacteria to extra- and intracellular habitats
journal, March 2012


Allene ether Nazarov cyclization
journal, January 2014


Novel salvage of queuine from queuosine and absence of queuine synthesis in Chlorella pyrenoidosa and Chlamydomonas reinhardtii.
journal, December 1988


Database resources of the National Center for Biotechnology Information
journal, January 2006


A Novel Class of Modular Transporters for Vitamins in Prokaryotes
journal, October 2008

  • Rodionov, D. A.; Hebbeln, P.; Eudes, A.
  • Journal of Bacteriology, Vol. 191, Issue 1
  • DOI: 10.1128/JB.01208-08

Cellular dynamics of tRNAs and their genes
journal, November 2009


Radical S -Adenosylmethionine Enzymes
journal, January 2014

  • Broderick, Joan B.; Duffus, Benjamin R.; Duschene, Kaitlin S.
  • Chemical Reviews, Vol. 114, Issue 8
  • DOI: 10.1021/cr4004709

The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes
journal, September 2005


BREX is a novel phage resistance system widespread in microbial genomes
journal, December 2014


Clostridium difficile Biofilm: Remodeling Metabolism and Cell Surface to Build a Sparse and Heterogeneously Aggregated Architecture
journal, September 2018


Crystal structure of tRNA-guanine transglycosylase: RNA modification by base exchange.
journal, June 1996


Synthesis of the Transfer-RNA Nucleoside Queuosine by Using a Chiral Allyl Azide Intermediate
journal, March 2007

  • Klepper, Florian; Jahn, Eva-Maria; Hickmann, Volker
  • Angewandte Chemie International Edition, Vol. 46, Issue 13
  • DOI: 10.1002/anie.200604579

UniProt: a worldwide hub of protein knowledge
November 2018


Presence of queuine in Drosophila melanogaster: correlation of free pool with queuosine content of tRNA and effect of mutations in pteridine metabolism
journal, January 1981

  • Jacobson, K. Bruce; Farkas, W. R.; Katze, J. R.
  • Nucleic Acids Research, Vol. 9, Issue 10
  • DOI: 10.1093/nar/9.10.2351

PROMALS3D: a tool for multiple protein sequence and structure alignments
journal, February 2008

  • Pei, Jimin; Kim, Bong-Hyun; Grishin, Nick V.
  • Nucleic Acids Research, Vol. 36, Issue 7
  • DOI: 10.1093/nar/gkn072

‘Democratized’ genomic enzymology web tools for functional assignment
journal, December 2018


A riboswitch selective for the queuosine precursor preQ1 contains an unusually small aptamer domain
journal, March 2007

  • Roth, Adam; Winkler, Wade C.; Regulski, Elizabeth E.
  • Nature Structural & Molecular Biology, Vol. 14, Issue 4
  • DOI: 10.1038/nsmb1224

Queuosine Formation in Eukaryotic tRNA Occurs via a Mitochondria-localized Heteromeric Transglycosylase
journal, May 2009

  • Boland, Coilin; Hayes, Patti; Santa-Maria, Ismael
  • Journal of Biological Chemistry, Vol. 284, Issue 27
  • DOI: 10.1074/jbc.M109.002477

PreQ0 Base, an Unusual Metabolite with Anti-cancer Activity from Streptomyces qinglanensis 172205
journal, March 2015


Structural Basis for Methyl Transfer by a Radical SAM Enzyme
journal, April 2011


A Role for tRNA Modifications in Genome Structure and Codon Usage
journal, March 2012


Diet-dependent depletion of queuosine in tRNAs in Caenorhabditis elegans does not lead to a developmental block
journal, June 2007


Micronutrient Requirements and Sharing Capabilities of the Human Gut Microbiome
journal, June 2019

  • Rodionov, Dmitry A.; Arzamasov, Aleksandr A.; Khoroshkin, Matvei S.
  • Frontiers in Microbiology, Vol. 10
  • DOI: 10.3389/fmicb.2019.01316

Structural, Functional, and Taxonomic Diversity of Three PreQ1 Riboswitch Classes
journal, July 2014


The Radical SAM Superfamily
journal, January 2008

  • Frey, Perry A.; Hegeman, Adrian D.; Ruzicka, Frank J.
  • Critical Reviews in Biochemistry and Molecular Biology, Vol. 43, Issue 1
  • DOI: 10.1080/10409230701829169

Effect of diet on the queuosine family of tRNAs of germ-free mice.
journal, July 1980


Administration of exogenous queuine is essential for the biosynthesis of the queuosine-containing transfer RNAs in the mouse.
journal, November 1981


Isolation and characterization of an Escherichia coli mutant lacking tRNA-guanine transglycosylase. Function and biosynthesis of queuosine in tRNA.
journal, June 1982


Database resources of the National Center for Biotechnology Information
journal, October 2020

  • Sayers, Eric W.; Beck, Jeffrey; Bolton, Evan E.
  • Nucleic Acids Research, Vol. 49, Issue D1
  • DOI: 10.1093/nar/gkaa892

Database resources of the National Center for Biotechnology Information
journal, December 2007

  • Wheeler, D. L.; Barrett, T.; Benson, D. A.
  • Nucleic Acids Research, Vol. 36, Issue Database
  • DOI: 10.1093/nar/gkm1000