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Riboneogenesis in yeast.

Cell | Jun 10, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21663798

Glucose is catabolized in yeast via two fundamental routes, glycolysis and the oxidative pentose phosphate pathway, which produces NADPH and the essential nucleotide component ribose-5-phosphate. Here, we describe riboneogenesis, a thermodynamically driven pathway that converts glycolytic intermediates into ribose-5-phosphate without production of NADPH. Riboneogenesis begins with synthesis, by the combined action of transketolase and aldolase, of the seven-carbon bisphosphorylated sugar sedoheptulose-1,7-bisphosphate. In the pathway's committed step, sedoheptulose bisphosphate is hydrolyzed to sedoheptulose-7-phosphate by the enzyme sedoheptulose-1,7-bisphosphatase (SHB17), whose activity we identified based on metabolomic analysis of the corresponding knockout strain. The crystal structure of Shb17 in complex with sedoheptulose-1,7-bisphosphate reveals that the substrate binds in the closed furan form in the active site. Sedoheptulose-7-phosphate is ultimately converted by known enzymes of the nonoxidative pentose phosphate pathway to ribose-5-phosphate. Flux through SHB17 increases when ribose demand is high relative to demand for NADPH, including during ribosome biogenesis in metabolically synchronized yeast cells.

Pubmed ID: 21663798 RIS Download

Mesh terms: Biosynthetic Pathways | Crystallography, X-Ray | Gene Deletion | Models, Molecular | Pentose Phosphate Pathway | Phosphoric Monoester Hydrolases | Ribosemonophosphates | Saccharomyces cerevisiae

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI078063
  • Agency: NIGMS NIH HHS, Id: GM071508
  • Agency: NIGMS NIH HHS, Id: P50 GM071508
  • Agency: NIGMS NIH HHS, Id: P50 GM071508-05
  • Agency: NIGMS NIH HHS, Id: P50 GM071508-06
  • Agency: NIGMS NIH HHS, Id: P50 GM071508-06S1
  • Agency: NIGMS NIH HHS, Id: P50 GM071508-07
  • Agency: NIGMS NIH HHS, Id: P50 GM071508-08
  • Agency: NIAID NIH HHS, Id: R01 AI078063
  • Agency: NIAID NIH HHS, Id: R01 AI078063-01
  • Agency: NIAID NIH HHS, Id: R01 AI078063-02
  • Agency: NIAID NIH HHS, Id: R01 AI078063-03
  • Agency: NIAID NIH HHS, Id: R01 AI078063-04

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