Erythritol feeds the pentose phosphate pathway via three new isomerases leading to D-erythrose-4-phosphate in Brucella

Thibault Barbier, François Collard, Amaia Zúñiga-Ripa, Ignacio Moriyón, Thibault Godard, Judith Becker, Christoph Wittmann, Emile Van Schaftingen, Jean-Jacques Letesson

Research output: Contribution to journalArticle

Abstract

Erythritol is an important nutrient for several α-2 Proteobacteria, including N2-fixing plant endosymbionts and Brucella, a worldwide pathogen that finds this four-carbon polyol in genital tissues. Erythritol metabolism involves phosphorylation to L-erythritol-4-phosphate by the kinase EryA and oxidation of the latter to L-3-tetrulose 4-phosphate by the dehydrogenase EryB. It is accepted that further steps involve oxidation by the putative dehydrogenase EryC and subsequent decarboxylation to yield triose-phosphates. Accordingly, growth on erythritol as the sole C source should require aldolase and fructose-1,6-bisphosphatase to produce essential hexose-6-monophosphate. However, we observed that a mutant devoid of fructose-1,6-bisphosphatases grew normally on erythritol and that EryC, which was assumed to be a dehydrogenase, actually belongs to the xylose isomerase superfamily. Moreover, we found that TpiA2 and RpiB, distant homologs of triose phosphate isomerase and ribose 5-phosphate isomerase B, were necessary, as previously shown for Rhizobium. By using purified recombinant enzymes, we demonstrated that L-3-tetrulose-4-phosphate was converted to D-erythrose 4-phosphate through three previously unknown isomerization reactions catalyzed by EryC (tetrulose-4-phosphate racemase), TpiA2 (D-3-tetrulose-4-phosphate isomerase; renamed EryH), and RpiB (D-erythrose-4-phosphate isomerase; renamed EryI), a pathway fully consistent with the isotopomer distribution of the erythrose-4-phosphate-derived amino acids phenylalanine and tyrosine obtained from bacteria grown on 13C-labeled erythritol. D-Erythrose-4-phosphate is then converted by enzymes of the pentose phosphate pathway to glyceraldehyde 3-phosphate and fructose 6-phosphate, thus bypassing fructose-1,6-bisphosphatase. This is the first description to our knowledge of a route feeding carbohydrate metabolism exclusively via D-erythrose 4-phosphate, a pathway that may provide clues to the preferential metabolism of erythritol by Brucella and its role in pathogenicity.

Original languageEnglish
Pages (from-to)17815-17820
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number50
DOIs
Publication statusPublished - 16 Dec 2014

Keywords

  • Alphaproteobacteria
  • Brucella
  • Erythritol
  • Pentose phosphate cycle
  • Tetrose metabolism

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  • Student Theses

    Revision of the erythritol catabolic pathway and of the central metabolism of the pathogen Brucella

    Author: Barbier, T., 14 Nov 2015

    Supervisor: Letesson, J. (Supervisor), Jadot, M. (President), Van Scaftingen, E. (External person) (Jury), Moriyón, I. (External person) (Jury) & Neyrolle, O. (External person) (Jury)

    Student thesis: Doc typesDoctor of Sciences

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