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.
riboneogenesis
NCBI PubMed ID: 21663798Publication DOI: 10.1016/j.cell.2011.05.022Journal NLM ID: 0413066Publisher: Cambridge, MA: Cell Press
Correspondence: Rabinowitz JD
; Caudy AA
Institutions: Lewis-Sigler Institute for Integrative Genomics, Department of Chemistry, Princeton University, Princeton, USA, Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Canada, Department of Chemistry, University of Tennessee, Knoxville, USA, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Canada
Methods: crystallography, extraction, cell growth, LC-MS/MS, HPLC-MS, enzymatic assay
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