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Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species

Folates are tripartite molecules comprising pterin, para-aminobenzoate (PABA), and glutamate moieties, which are essential cofactors involved in DNA and amino acid synthesis. The obligately intracellular Chlamydia species have lost several biosynthetic pathways for essential nutrients which they can...

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Autores principales: Adams, Nancy E., Thiaville, Jennifer J., Proestos, James, Juárez-Vázquez, Ana L., McCoy, Andrea J., Barona-Gómez, Francisco, Iwata-Reuyl, Dirk, de Crécy-Lagard, Valérie, Maurelli, Anthony T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161248/
https://www.ncbi.nlm.nih.gov/pubmed/25006229
http://dx.doi.org/10.1128/mBio.01378-14
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author Adams, Nancy E.
Thiaville, Jennifer J.
Proestos, James
Juárez-Vázquez, Ana L.
McCoy, Andrea J.
Barona-Gómez, Francisco
Iwata-Reuyl, Dirk
de Crécy-Lagard, Valérie
Maurelli, Anthony T.
author_facet Adams, Nancy E.
Thiaville, Jennifer J.
Proestos, James
Juárez-Vázquez, Ana L.
McCoy, Andrea J.
Barona-Gómez, Francisco
Iwata-Reuyl, Dirk
de Crécy-Lagard, Valérie
Maurelli, Anthony T.
author_sort Adams, Nancy E.
collection PubMed
description Folates are tripartite molecules comprising pterin, para-aminobenzoate (PABA), and glutamate moieties, which are essential cofactors involved in DNA and amino acid synthesis. The obligately intracellular Chlamydia species have lost several biosynthetic pathways for essential nutrients which they can obtain from their host but have retained the capacity to synthesize folate. In most bacteria, synthesis of the pterin moiety of folate requires the FolEQBK enzymes, while synthesis of the PABA moiety is carried out by the PabABC enzymes. Bioinformatic analyses reveal that while members of Chlamydia are missing the genes for FolE (GTP cyclohydrolase) and FolQ, which catalyze the initial steps in de novo synthesis of the pterin moiety, they have genes for the rest of the pterin pathway. We screened a chlamydial genomic library in deletion mutants of Escherichia coli to identify the “missing genes” and identified a novel enzyme, TrpF(CtL2), which has broad substrate specificity. TrpF(CtL2), in combination with GTP cyclohydrolase II (RibA), the first enzyme of riboflavin synthesis, provides a bypass of the first two canonical steps in folate synthesis catalyzed by FolE and FolQ. Notably, TrpF(CtL2) retains the phosphoribosyl anthranilate isomerase activity of the original annotation. Additionally, we independently confirmed the recent discovery of a novel enzyme, CT610, which uses an unknown precursor to synthesize PABA and complements E. coli mutants with deletions of pabA, pabB, or pabC. Thus, Chlamydia species have evolved a variant folate synthesis pathway that employs a patchwork of promiscuous and adaptable enzymes recruited from other biosynthetic pathways.
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spelling pubmed-41612482014-09-11 Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species Adams, Nancy E. Thiaville, Jennifer J. Proestos, James Juárez-Vázquez, Ana L. McCoy, Andrea J. Barona-Gómez, Francisco Iwata-Reuyl, Dirk de Crécy-Lagard, Valérie Maurelli, Anthony T. mBio Research Article Folates are tripartite molecules comprising pterin, para-aminobenzoate (PABA), and glutamate moieties, which are essential cofactors involved in DNA and amino acid synthesis. The obligately intracellular Chlamydia species have lost several biosynthetic pathways for essential nutrients which they can obtain from their host but have retained the capacity to synthesize folate. In most bacteria, synthesis of the pterin moiety of folate requires the FolEQBK enzymes, while synthesis of the PABA moiety is carried out by the PabABC enzymes. Bioinformatic analyses reveal that while members of Chlamydia are missing the genes for FolE (GTP cyclohydrolase) and FolQ, which catalyze the initial steps in de novo synthesis of the pterin moiety, they have genes for the rest of the pterin pathway. We screened a chlamydial genomic library in deletion mutants of Escherichia coli to identify the “missing genes” and identified a novel enzyme, TrpF(CtL2), which has broad substrate specificity. TrpF(CtL2), in combination with GTP cyclohydrolase II (RibA), the first enzyme of riboflavin synthesis, provides a bypass of the first two canonical steps in folate synthesis catalyzed by FolE and FolQ. Notably, TrpF(CtL2) retains the phosphoribosyl anthranilate isomerase activity of the original annotation. Additionally, we independently confirmed the recent discovery of a novel enzyme, CT610, which uses an unknown precursor to synthesize PABA and complements E. coli mutants with deletions of pabA, pabB, or pabC. Thus, Chlamydia species have evolved a variant folate synthesis pathway that employs a patchwork of promiscuous and adaptable enzymes recruited from other biosynthetic pathways. American Society of Microbiology 2014-07-08 /pmc/articles/PMC4161248/ /pubmed/25006229 http://dx.doi.org/10.1128/mBio.01378-14 Text en Copyright © 2014 Adams et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Adams, Nancy E.
Thiaville, Jennifer J.
Proestos, James
Juárez-Vázquez, Ana L.
McCoy, Andrea J.
Barona-Gómez, Francisco
Iwata-Reuyl, Dirk
de Crécy-Lagard, Valérie
Maurelli, Anthony T.
Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title_full Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title_fullStr Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title_full_unstemmed Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title_short Promiscuous and Adaptable Enzymes Fill “Holes” in the Tetrahydrofolate Pathway in Chlamydia Species
title_sort promiscuous and adaptable enzymes fill “holes” in the tetrahydrofolate pathway in chlamydia species
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161248/
https://www.ncbi.nlm.nih.gov/pubmed/25006229
http://dx.doi.org/10.1128/mBio.01378-14
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