Riboneogenesis in yeast |
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Authors: | Clasquin Michelle F Melamud Eugene Singer Alexander Gooding Jessica R Xu Xiaohui Dong Aiping Cui Hong Campagna Shawn R Savchenko Alexei Yakunin Alexander F Rabinowitz Joshua D Caudy Amy A |
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Institution: | 1 Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544, USA 2 Department of Chemistry, Princeton University, Princeton NJ 08544, USA 3 Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto M5G 1L6, Canada 4 Department of Chemistry, University of Tennessee, Knoxville, TN 37996, USA |
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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. |
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