title: Riboneogenesis in yeast.
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.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544, USA.
authors.forename: Michelle F
authors.initials: MF
authors.lastname: Clasquin
authors.forename: Eugene
authors.initials: E
authors.lastname: Melamud
authors.forename: Alexander
authors.initials: A
authors.lastname: Singer
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Gooding
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xu
authors.forename: Aiping
authors.initials: A
authors.lastname: Dong
authors.forename: Hong
authors.initials: H
authors.lastname: Cui
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Campagna
authors.forename: Alexei
authors.initials: A
authors.lastname: Savchenko
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Yakunin
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Amy A
authors.initials: AA
authors.lastname: Caudy
mesh_terms: D053898:Biosynthetic Pathways; D018360:Crystallography, X-Ray; D017353:Gene Deletion; D008958:Models, Molecular; D010427:Pentose Phosphate Pathway; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012267:Ribosemonophosphates / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*
chemical_list: D012267:Ribosemonophosphates; C031626:ribose-5-phosphate; D010744:Phosphoric Monoester Hydrolases; C022627:sedoheptulose-bisphosphatase