Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Entner-Doudoroff (ED) pathway is a classic central pathway of d-glucose metabolism in all three phylogenetic domains. On the other hand, Archaea and/or bacteria possess several modified versions of the ED pathway, in which nonphosphorylated intermediates are involved. Several fungi, including Pichia stipitis and Debaryomyces hansenii, possess an alternative pathway of L-rhamnose metabolism, which is different from the known bacterial pathway. Gene cluster related to this hypothetical pathway was identified by bioinformatic analysis using the metabolic enzymes involved in analogous sugar pathways to the ED pathway. Furthermore, the homologous gene cluster was found not only in many other fungi but also several bacteria, including Azotobacter vinelandii. Four putative metabolic genes, LRA1-4, were cloned, overexpressed in Escherichia coli, and purified. Substrate specificity and kinetic analysis revealed that nonphosphorylated intermediates related to L-rhamnose are significant active substrates for the purified LRA1-4 proteins. Furthermore, L-2-keto-3-deoxyrhamnonate was structurally identified as both reaction products of dehydration by LRA3 and aldol condensation by LRA4. These results suggested that the LRA1-4 genes encode L-rhamnose 1-dehydrogenase, L-rhamnono-gamma-lactonase, L-rhamnonate dehydratase, and L-KDR aldolase, respectively, by which L-rhamnose is converted into pyruvate and L-lactaldehyde through analogous reaction steps to the ED pathway. There was no evolutionary relationship between L-KDR aldolases from fungi and bacteria.
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PMID:Eukaryotic and bacterial gene clusters related to an alternative pathway of nonphosphorylated L-rhamnose metabolism. 1850 28

Several bacteria, including Azotobacter vinelandii, possess an alternative pathway of L-rhamnose metabolism, which is different from the known bacterial pathway. In a previous article, a gene cluster related to this pathway was identified, consisting of the genes encoding the four metabolic enzymes L-rhamnose-1-dehydrogenase (LRA1), L-rhamnono-gamma-lactonase (LRA2), L-rhamnonate dehydratase (LRA3) and L-2-keto-3-deoxyrhamnonate (L-KDR) aldolase (LRA4), by which L-rhamnose is converted into pyruvate and L-lactaldehyde, through analogous reaction steps to the well-known Entner-Doudoroff (ED) pathway. In this study, bioinformatic analysis revealed that Sphingomonas sp. possesses a gene cluster consisting of LRA1-3 and two genes of unknown function, LRA5 and LRA6. LRA5 catalyzed the NAD(+)-dependent dehydrogenation of several L-2-keto-3-deoxyacid-sugars, including L-KDR. Furthermore, the reaction product was converted to pyruvate and L-lactate by LRA6; this is different from the pathway of Azotobacter vinelandii. Therefore, LRA5 and LRA6 were assigned as the novel enzymes L-KDR 4-dehydrogenase and L-2,4-diketo-3-deoxyrhamnonate hydrolase, respectively. Interestingly, both enzymes were phylogenetically similar to L-rhamnose-1-dehydrogenase and D-2-keto-3-deoxyarabinonate dehydratase, respectively, and the latter was involved in the archeal nonphosphorylative d-arabinose pathway, which is partially analogous to the ED pathway. The introduction of LRA1-4 or LRA1-3, LRA5 and LAR6 compensated for the L-rhamnose-defective phenotype of an Escherichia coli mutant. Metabolic evolution and promiscuity between the alternative l-rhamnose pathway and other sugar pathways analogous to the ED pathway are discussed.
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PMID:Novel modified version of nonphosphorylated sugar metabolism--an alternative L-rhamnose pathway of Sphingomonas sp. 1918 28