Riboneogenesis in yeast

Michelle F. Clasquin, Eugene Melamud, Alexander Singer, Jessica R. Gooding, Xiaohui Xu, Aiping Dong, Hong Cui, Shawn R. Campagna, Alexei Savchenko, Alexander F. Yakunin, Joshua D. Rabinowitz, Amy A. Caudy

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)969-980
Number of pages12
JournalCell
Volume145
Issue number6
DOIs
StatePublished - Jun 10 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Clasquin, M. F., Melamud, E., Singer, A., Gooding, J. R., Xu, X., Dong, A., Cui, H., Campagna, S. R., Savchenko, A., Yakunin, A. F., Rabinowitz, J. D., & Caudy, A. A. (2011). Riboneogenesis in yeast. Cell, 145(6), 969-980. https://doi.org/10.1016/j.cell.2011.05.022