Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 50, Pages 17815-17820Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1414622111
Keywords
Brucella; erythritol; alphaproteobacteria; pentose phosphate cycle; tetrose metabolism
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Funding
- Welbio grant of the Walloon Region
- Fonds de la Recherche Scientifique Medicale
- FNRS (Fonds National de la Recherche Scientifique) grant (Fonds de la Recherche Fondamentale Collective Grant) [2452110]
- Belgian Science Policy Office
- Aspirant FNRS
- Ministerio de Economia y Competitividad of Spain [AGL2011-30453-C04-00]
- Fundacion para la Investigacion Medica Aplicada
- FIMA
- German Research Foundation through Schwerpunktprogramm [1316]
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Erythritol is an important nutrient for several alpha-2 Proteobacteria, including N-2-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-4phosphate racemase), TpiA2 (D-3-tetrulose-4-phosphate isomerase; renamed EryH), and RpiB (D-erythrose-4-phosphate isomerase; renamed Eryl), a pathway fully consistent with the isotopomer distribution of the erythrose-4-phosphate-derived amino acids phenylalanine and tyrosine obtained from bacteria grown on C-13-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.
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