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Riboneogenesis in yeast.

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

Authors

  • Clasquin MF
  • Melamud E
  • Singer A
  • Gooding JR
  • Xu X
  • Dong A
  • Cui H
  • Campagna SR
  • Savchenko A
  • Yakunin AF
  • Rabinowitz JD
  • Caudy AA

Journal

Cell

Publication Data

June 10, 2011

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

Mesh Terms

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