|Title||Riboneogenesis in yeast.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|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|
|Date Published||2011 Jun 10|
|Keywords||Biosynthetic Pathways, Crystallography, X-Ray, Gene Deletion, Models, Molecular, Pentose Phosphate Pathway, Phosphoric Monoester Hydrolases, Ribosemonophosphates, Saccharomyces cerevisiae|
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.