Riboneogenesis in yeast. Author Michelle Clasquin, Eugene Melamud, Alexander Singer, Jessica Gooding, Xiaohui Xu, Aiping Dong, Hong Cui, Shawn Campagna, Alexei Savchenko, Alexander Yakunin, Joshua Rabinowitz, Amy Caudy Publication Year 2011 Type Journal Article Abstract 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. Keywords Gene Deletion, Saccharomyces cerevisiae, Crystallography, X-Ray, Models, Molecular, Phosphoric Monoester Hydrolases, Biosynthetic Pathways, Pentose Phosphate Pathway, Ribosemonophosphates Journal Cell Volume 145 Issue 6 Pages 969-80 Date Published 06/2011 Alternate Journal Cell Google ScholarBibTeXEndNote X3 XML