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MetaCyc Pathway: 4-deoxy-L-threo-hex-4-enopyranuronate degradation
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: 4-deoxy-L-threo-hex-4-enopyranuronate degradation

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: 5-dehydro-4-deoxy-D-glucuronate degradation

Superclasses: Degradation/Utilization/AssimilationSecondary Metabolites DegradationSugar Derivatives Degradation

Some taxa known to possess this pathway include : Dickeya dadantii 3937, Erwinia chrysanthemi EC16, Escherichia coli K-12 substr. MG1655, Pectobacterium carotovorum, Pseudomonas sp., Streptococcus agalactiae NEM316

Expected Taxonomic Range: Bacteria

General Background

Many organisms produce large complex polymers that contain uronic acids. A few examples include pectin, an important component of plant cell walls that contains D-galacturonate, and glycosaminoglycans produced by animals, which include heparin, heparan sulfate, hyaluronan, chondroitin sulfate etc.

The bacterial degradation pathways for these polymers usually invovle an intial attack on the polymer that breaks it into short oligosaccharides. Two main types of enzymes that perform this task are the hydrolases and the endolyases. While hydrolases produce oligosaccharides that contain sugar residues similar to those in the polymer, lyases produce oligosaccharides that have a 4-5 unsaturated uronic acid at their non-reducing end. This is typically followed by the action of exolyases or hydrolases that cleave the oligosaccharides, resulting in the production of unstable unsaturated mono uronic acid monomers. Two forms of unsaturated uronic acids are formed, depending on the stereochemistry of the original acid - 4-deoxy-L-erythro-hex-4-enopyranuronate and 4-deoxy-L-threo-hex-4-enopyranuronate. The degradation of many polymers, including gellan, rhamnogalacturan, pectin, heparin, heparan sulfate, dermatan sulfate, hyaluronan and chondroitin results in formation the latter. 4-deoxy-L-threo-hex-4-enopyranuronate is unstable and the ring opens spontaneously, forming the keto acid 5-dehydro-4-deoxy-D-glucuronate. This pathway describes the degradation of that intermediate to metabolites of central metabolism.

About This Pathway

The pathway, which was first studied in detail in the pectin degrader Dickeya chrysanthemi, begins with the isomerization of 5-dehydro-4-deoxy-D-glucuronate (DKI) to 3-deoxy-D-glycero-2,5-hexodiulosonate (DKII). The kduI gene encoding the isomerase has been identified in this organism [Condemine91], but the enzyme has not been characterized. Earlier work characterized this enzyme in a pseudomonad [Preiss63]. 3-deoxy-D-glycero-2,5-hexodiulosonate is reduced to the common metabolite 2-dehydro-3-deoxy-D-gluconate, a compound that is also an intermediate in D-galacturonate degradation I. 2-dehydro-3-deoxy-D-gluconate is phosphorylated and then cleaved by an aldolase encoded by the kdgA gene, producing the central metabolites D-glyceraldehyde 3-phosphate and pyruvate.

The same pathway has also been characterized from the heparin/hyaluronan-degradating bacterium Streptococcus agalactiae NEM316 [Maruyama15]. Two of the enzymes ( EC, 5-dehydro-4-deoxy-D-glucuronate isomerase and EC, 2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase) have been characterized in detail from this organism. While their actions are identical to those of the Dickeya chrysanthemi enzymes, they share very little sequence similarity and possess different structures, suggesting parallel evolution. The kduI and kduD genes are found in enterococci and clostridia, while the dhuI and dhuD genes are much less common and found primarily in streptococci [Maruyama15].

In Escherichia coli the aldolase encoded by gene eda is involved in the Entner-Doudoroff pathway I. However, in Dickeya chrysanthemi this enzyme does not appear to be involved in D-gluconate catabolism and no product of the edd gene that encodes the phosphogluconate dehydratase could be detected in various species of Erwinia. These observations question the existence of the Entner-Doudoroff pathway in these organisms ( [HugouvieuxCotte94, HugouvieuxCotte96].

Most of the enzymes in this pathway are controlled by kdgR a transcriptional regulator that is induced by 2-dehydro-3-deoxy-D-gluconate [Reverchon91, Nasser91]. A comparative genomics analysis of the kdgR regulon in eight enterobacteria including Dickeya dadantii 3937 and Pectobacterium carotovorum and two members of the genus Vibrio, yielded a metabolic map of pectin and pectin-derivative degradation in these organisms [Rodionov04a].

Superpathways: superpathway of microbial D-galacturonate and D-glucuronate degradation

Relationship Links: KEGG:PART-OF:map00040

Created 30-Apr-2010 by Fulcher CA, SRI International
Revised 16-Mar-2015 by Caspi R, SRI International


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Blot02: Blot N, Berrier C, Hugouvieux-Cotte-Pattat N, Ghazi A, Condemine G (2002). "The oligogalacturonate-specific porin KdgM of Erwinia chrysanthemi belongs to a new porin family." J Biol Chem 277(10);7936-44. PMID: 11773048

Caffall09: Caffall KH, Mohnen D (2009). "The structure, function, and biosynthesis of plant cell wall pectic polysaccharides." Carbohydr Res 344(14);1879-900. PMID: 19616198

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Condemine91: Condemine G, Robert-Baudouy J (1991). "Analysis of an Erwinia chrysanthemi gene cluster involved in pectin degradation." Mol Microbiol 1991;5(9);2191-202. PMID: 1766386

Fraser97: Fraser JR, Laurent TC, Laurent UB (1997). "Hyaluronan: its nature, distribution, functions and turnover." J Intern Med 242(1);27-33. PMID: 9260563

Gallagher01a: Gallagher JT (2001). "Heparan sulfate: growth control with a restricted sequence menu." J Clin Invest 108(3);357-61. PMID: 11489926

Gatti79: Gatti, G., Casu, B., Hamer, G. K., Pelin, A. S. (1979). Macromolecules 12:1001-1007.

Girish07: Girish KS, Kemparaju K (2007). "The magic glue hyaluronan and its eraser hyaluronidase: a biological overview." Life Sci 80(21);1921-43. PMID: 17408700

Hovingh70: Hovingh P, Linker A (1970). "The enzymatic degradation of heparin and heparitin sulfate. 3. Purification of a heparitinase and a heparinase from flavobacteria." J Biol Chem 245(22);6170-5. PMID: 5484472

HugouvieuxCotte94: Hugouvieux-Cotte-Pattat N, Robert-Baudouy J (1994). "Molecular analysis of the Erwinia chrysanthemi region containing the kdgA and zwf genes." Mol Microbiol 11(1);67-75. PMID: 8145647

HugouvieuxCotte96: Hugouvieux-Cotte-Pattat N, Condemine G, Nasser W, Reverchon S (1996). "Regulation of pectinolysis in Erwinia chrysanthemi." Annu Rev Microbiol 50;213-57. PMID: 8905080

Lindahl78: Lindahl U, Hook M (1978). "Glycosaminoglycans and their binding to biological macromolecules." Annu Rev Biochem 47;385-417. PMID: 354500

MartensUzunova09: Martens-Uzunova ES, Schaap PJ (2009). "Assessment of the pectin degrading enzyme network of Aspergillus niger by functional genomics." Fungal Genet Biol 46 Suppl 1;S170-S179. PMID: 19618506

Maruyama15: Maruyama Y, Oiki S, Takase R, Mikami B, Murata K, Hashimoto W (2015). "Metabolic Fate of Unsaturated Glucuronic/Iduronic Acids from Glycosaminoglycans: Molecular identification and structure determination of streptococcal isomerase and dehydrogenase." J Biol Chem 290(10);6281-92. PMID: 25605731

Murphy04: Murphy KJ, Merry CL, Lyon M, Thompson JE, Roberts IS, Gallagher JT (2004). "A new model for the domain structure of heparan sulfate based on the novel specificity of K5 lyase." J Biol Chem 279(26);27239-45. PMID: 15047699

Nasser91: Nasser W, Condemine G, Plantier R, Anker D, Robert-Baudouy J (1991). "Inducing properties of analogs of 2-keto-3-deoxygluconate on the expression of pectinase genes of Erwinia chrysanthemi." FEMS Microbiol Lett 65(1);73-8. PMID: 1874406

Preiss63: Preiss J, Ashwell G (1963). "Polygalacturonic acid metabolism in bacteria. II. Formation and metabolism of 3-deoxy-D-glycero-2, 5-hexodiulosonic acid." J Biol Chem 238;1577-83. PMID: 13986017

Reginault08: Reginault, Ph., Valette-Collet , O., Boccara, M. (2008). "The importance of fungal pectinolytic enzymes in plant invasion, host adaptability and symptom type." Eur. J. Plant Pathol.

Reverchon91: Reverchon S, Nasser W, Robert-Baudouy J (1991). "Characterization of kdgR, a gene of Erwinia chrysanthemi that regulates pectin degradation." Mol Microbiol 5(9);2203-16. PMID: 1840643

Richard09: Richard P, Hilditch S (2009). "D-galacturonic acid catabolism in microorganisms and its biotechnological relevance." Appl Microbiol Biotechnol 82(4);597-604. PMID: 19159926

Rodionov04a: Rodionov DA, Gelfand MS, Hugouvieux-Cotte-Pattat N (2004). "Comparative genomics of the KdgR regulon in Erwinia chrysanthemi 3937 and other gamma-proteobacteria." Microbiology 150(Pt 11);3571-90. PMID: 15528647

Rosenberg97: Rosenberg RD, Shworak NW, Liu J, Schwartz JJ, Zhang L (1997). "Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated?." J Clin Invest 99(9);2062-70. PMID: 9151776

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Condemine84: Condemine G, Hugouvieux-Cotte-Pattat N, Robert-Baudouy J (1984). "An enzyme in the pectinolytic pathway of Erwinia chrysanthemi: 2-keto-3-deoxygluconate oxidoreductase." Journal of General Microbiology 130, 2839-2844.

Condemine86: Condemine G, Hugouvieux-Cotte-Pattat N, Robert-Baudouy J (1986). "Isolation of Erwinia chrysanthemi kduD mutants altered in pectin degradation." J Bacteriol 165(3);937-41. PMID: 3949717

Crowther05: Crowther RL, Georgiadis MM (2005). "The crystal structure of 5-keto-4-deoxyuronate isomerase from Escherichia coli." Proteins 61(3);680-4. PMID: 16152643

Cynkin60: Cynkin MA, Ashwell G (1960). "Uronic acid metabolism in bacteria. IV. Purification and properties of 2-keto-3-deoxy-D-gluconokinase in Escherichia coli." J Biol Chem 235;1576-9. PMID: 13813474

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dunten98: Dunten P, Jaffe H, Aksamit RR (1998). "Crystallization of 5-keto-4-deoxyuronate isomerase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 54(Pt 4);678-80. PMID: 9761873

Egan92: Egan SE, Fliege R, Tong S, Shibata A, Wolf RE, Conway T (1992). "Molecular characterization of the Entner-Doudoroff pathway in Escherichia coli: sequence analysis and localization of promoters for the edd-eda operon." J Bacteriol 1992;174(14);4638-46. PMID: 1624451

Fradkin71: Fradkin JE, Fraenkel DG (1971). "2-keto-3-deoxygluconate 6-phosphate aldolase mutants of Escherichia coli." J Bacteriol 108(3);1277-83. PMID: 4945194

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Griffiths02: Griffiths JS, Wymer NJ, Njolito E, Niranjanakumari S, Fierke CA, Toone EJ (2002). "Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase." Bioorg Med Chem 10(3);545-50. PMID: 11814840

Hannemann07: Hannemann F, Bernhardt R, Jose J (2007). "Biocatalytic synthesis of 4-pregnen-20,21-diol-3-one, a selective inhibitor of human 5alpha-reductase type II." J Enzyme Inhib Med Chem 22(5);570-6. PMID: 18035825

Hu10: Hu W, Tedesco S, McDonagh B, Barcena JA, Keane C, Sheehan D (2010). "Selection of thiol- and disulfide-containing proteins of Escherichia coli on activated thiol-Sepharose." Anal Biochem 398(2);245-53. PMID: 19903445

HugouvieuxCotte94a: Hugouvieux-Cotte-Pattat N, Nasser W, Robert-Baudouy J (1994). "Molecular characterization of the Erwinia chrysanthemi kdgK gene involved in pectin degradation." J Bacteriol 176(8);2386-92. PMID: 8157608

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Kim06a: Kim S, Lee SB (2006). "Characterization of Sulfolobus solfataricus 2-keto-3-deoxy-D-gluconate kinase in the modified Entner-Doudoroff pathway." Biosci Biotechnol Biochem 70(6);1308-16. PMID: 16794308

Lamble05: Lamble HJ, Theodossis A, Milburn CC, Taylor GL, Bull SD, Hough DW, Danson MJ (2005). "Promiscuity in the part-phosphorylative Entner-Doudoroff pathway of the archaeon Sulfolobus solfataricus." FEBS Lett 579(30);6865-9. PMID: 16330030

Showing only 20 references. To show more, press the button "Show all references".

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sun May 1, 2016, biocyc14.