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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: rutin degradation

Enzyme View:

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: rutin catabolic pathway

Superclasses: Degradation/Utilization/Assimilation Secondary Metabolites Degradation Flavonoids Degradation

Some taxa known to possess this pathway include ? : Aspergillus flavus , Aspergillus flavus NRRL3357 , Aspergillus japonicus , Aspergillus niger , Penicillium olsonii

Expected Taxonomic Range: Fungi

Summary:
General Background

This pathway represents the oxidative degradation of flavonols such as rutin (a glycoside) and quercetin by fungi. Flavonols are secondary metabolites found in abundance in plant tissues and exudates. This pathway for rutin degradation (commonly named the rutin catabolic pathway) was first studied in fungi over fifty years ago [WESTLAKE59, HATTORI59] and the entire pathway was enzymologically characterized in the mold Aspergillus flavus [WESTLAKE59, WESTLAKE61, HAY61, WESTLAKE61a, Child63]. More recent research in this area has focused on the enzyme quercetin 2,3-dioxygenase (quercetinase) ([Fusetti02, Tranchimand08] and reviewed in [Tranchimand10]).

This pathway has been strictly proven only in molds (filamentous fungi). Various molds, including those from the genera Aspergillus and Penicillium can use rutin as a sole source of carbon and energy via this pathway. In molds all three enzymes have been characterized and their enzymatic activities are found extracellularly. The pathway is also probable in yeast-like fungi and yeasts based on metabolite detection studies, although the enzymatic activities were shown to be intracellular ([HATTORI59, Westlake66] and reviewed in [Tranchimand10]).

In bacteria, this pathway is less likely. Bacterial homologs of quercetinase have been characterized, such as the enzymes from Streptomyces sp. FLA [Merkens08, Merkens08a, Merkens07] and Bacillus subtilis [Bowater04, Barney04, Gopal05, Schaab06]. A pirin protein homolog yhhW in Escherichia coli was shown to possess quercetinase activity [Adams05] (see pirin-like protein). However, the bacterial quercetinases may function in detoxification rather than catabolism, and the remaining two enzymes of the pathway have not been reported in prokaryotes (reviewed in [Tranchimand10, Das06]).

About This Pathway

In the first step of this pathway a glycosidase hydrolyzes the disaccharide rutinose from the glycosylated flavonol rutin, producing the flavonol aglycone quercetin and rutinose. Because the second enzyme quercetinase cannot utilize 3-glycosylated flavonols, a glycosidase capable of deglycosylating a glycosylated flavonol is necessary. A glycosidase (rutinase) from Aspergillus flavus has been characterized [HAY61] and a β-rutinosidase from Talaromyces rugulosus has also been characterized [Narikawa00]. Both glycosidases were produced extracellularly. Other known extracellular glycosidases that could also potentially participate in this pathway, but have not been proven to participate, include β-glucosidase, α-L-rhamnosidase, and quercitrinase (EC 3.2.1.66) (reviewed in [Tranchimand10]).

The second enzyme in the rutin catabolic pathway is quercetin 2,3-dioxygenase (quercetinase) which catalyzes the conversion of quercetin to a depside (2-protocatechuoylphloroglucinolcarboxylate) and carbon monoxide (see [Child71] for a definition of depside). This enzyme has been relatively well studied (reviewed in [Tranchimand10]). Click on this enzyme in the pathway for a detailed summary.

The third enzyme of the rutin catabolic pathway is an esterase that hydrolyzes the depside 2-protocatechuoylphloroglucinolcarboxylate to its two corresponding phenolic acids phloroglucinol carboxylate and protocatechuate. These compounds can undergo ring cleavage and subsequent entry into central metabolism ([Halsall69] and reviewed in [Tranchimand10]).

Credits:
Created 28-Jul-2011 by Fulcher CA , SRI International


References

Adams05: Adams M, Jia Z (2005). "Structural and biochemical analysis reveal pirins to possess quercetinase activity." J Biol Chem 280(31);28675-82. PMID: 15951572

Barney04: Barney BM, Schaab MR, LoBrutto R, Francisco WA (2004). "Evidence for a new metal in a known active site: purification and characterization of an iron-containing quercetin 2,3-dioxygenase from Bacillus subtilis." Protein Expr Purif 35(1);131-41. PMID: 15039076

Bowater04: Bowater L, Fairhurst SA, Just VJ, Bornemann S (2004). "Bacillus subtilis YxaG is a novel Fe-containing quercetin 2,3-dioxygenase." FEBS Lett 557(1-3);45-8. PMID: 14741339

Child63: Child JJ, Simpson FJ, Westlake DWS (1963). "Degradation of rutin by Aspergillus flavus. Production, purification and characterization of an esterase." Can J Microbiol 9:653-664.

Child71: Child JJ, Oka T, Simpson FJ, Krishnamurty HG (1971). "Purification and properties of a phenol carboxylic acid acyl esterase from Aspergillus flavus." Can J Microbiol 17(11);1455-63. PMID: 5003249

Das06: Das S, Rosazza JP (2006). "Microbial and enzymatic transformations of flavonoids." J Nat Prod 69(3);499-508. PMID: 16562863

Fusetti02: Fusetti F, Schroter KH, Steiner RA, van Noort PI, Pijning T, Rozeboom HJ, Kalk KH, Egmond MR, Dijkstra BW (2002). "Crystal structure of the copper-containing quercetin 2,3-dioxygenase from Aspergillus japonicus." Structure 10(2);259-68. PMID: 11839311

Gopal05: Gopal B, Madan LL, Betz SF, Kossiakoff AA (2005). "The crystal structure of a quercetin 2,3-dioxygenase from Bacillus subtilis suggests modulation of enzyme activity by a change in the metal ion at the active site(s)." Biochemistry 44(1);193-201. PMID: 15628860

Halsall69: Halsall BE, Darrah JA, Cain RB (1969). "The regulation of enzymes of aromatic-ring fission in fungi: organisms using both catechol and protocatechuate pathways." Biochem J 114(4);75P-76P. PMID: 5343779

HATTORI59: HATTORI S, NOGUCHI I (1959). "Microbial degradation of rutin." Nature 184 (Suppl 15);1145-6. PMID: 13852047

HAY61: HAY GW, WESTLAKE DW, SIMPSON FJ (1961). "Degradation of rutin by Aspergillus flavus. Purification and characterization of rutinase." Can J Microbiol 7;921-32. PMID: 13905544

Merkens07: Merkens H, Sielker S, Rose K, Fetzner S (2007). "A new monocupin quercetinase of Streptomyces sp. FLA: identification and heterologous expression of the queD gene and activity of the recombinant enzyme towards different flavonols." Arch Microbiol 187(6);475-87. PMID: 17516049

Merkens08: Merkens H, Kappl R, Jakob RP, Schmid FX, Fetzner S (2008). "Quercetinase QueD of Streptomyces sp. FLA, a monocupin dioxygenase with a preference for nickel and cobalt." Biochemistry 47(46);12185-96. PMID: 18950192

Merkens08a: Merkens H, Fetzner S (2008). "Transcriptional analysis of the queD gene coding for quercetinase of Streptomyces sp. FLA." FEMS Microbiol Lett 287(1);100-7. PMID: 18681865

Narikawa00: Narikawa T, Shinoyama H, Fujii T (2000). "A beta-rutinosidase from Penicillium rugulosum IFO 7242 that is a peculiar flavonoid glycosidase." Biosci Biotechnol Biochem 64(6);1317-9. PMID: 10923813

Schaab06: Schaab MR, Barney BM, Francisco WA (2006). "Kinetic and spectroscopic studies on the quercetin 2,3-dioxygenase from Bacillus subtilis." Biochemistry 45(3);1009-16. PMID: 16411777

Tranchimand08: Tranchimand S, Ertel G, Gaydou V, Gaudin C, Tron T, Iacazio G (2008). "Biochemical and molecular characterization of a quercetinase from Penicillium olsonii." Biochimie 90(5);781-9. PMID: 18206655

Tranchimand10: Tranchimand S, Brouant P, Iacazio G (2010). "The rutin catabolic pathway with special emphasis on quercetinase." Biodegradation 21(6);833-59. PMID: 20419500

WESTLAKE59: WESTLAKE DW, TALBOT G, BLAKLEY ER, SIMPSON FJ (1959). "Microbiol decomposition of rutin." Can J Microbiol 5;621-9. PMID: 13844170

WESTLAKE61: WESTLAKE DW, ROXBURGH JM, TALBOT G (1961). "Microbial production of carbon monoxide from flavonoids." Nature 189;510-1. PMID: 13784623

WESTLAKE61a: WESTLAKE DW, SIMPSON FJ (1961). "Degradation of rutin by Aspergillus flavus. Factors affecting production of the enzyme system." Can J Microbiol 7;33-44. PMID: 13784624

Westlake66: Westlake DW, Spencer JF (1966). "The utilization of flavonoid compounds by yeasts and yeast-like fungi." Can J Microbiol 12(1);165-74. PMID: 5950962

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

Antonczak09: Antonczak S, Fiorucci S, Golebiowski J, Cabrol-Bass D (2009). "Theoretical investigations of the role played by quercetinase enzymes upon the flavonoids oxygenolysis mechanism." Phys Chem Chem Phys 11(10);1491-501. PMID: 19240925

Barath09: Barath G, Kaizer J, Speier G, Parkanyi L, Kuzmann E, Vertes A (2009). "One metal-two pathways to the carboxylate-enhanced, iron-containing quercetinase mimics." Chem Commun (Camb) (24);3630-2. PMID: 19521631

Baumgertel03: Baumgertel A, Grimm R, Eisenbeiss W, Kreis W (2003). "Purification and characterization of a flavonol 3-O-beta-heterodisaccharidase from the dried herb of Fagopyrum esculentum Moench." Phytochemistry 64(2);411-8. PMID: 12943757

Brown82: Brown SB, Rajananda V, Holroyd JA, Evans EG (1982). "A study of the mechanism of quercetin oxygenation by 18O labelling. A comparison of the mechanism with that of haem degradation." Biochem J 205(1);239-44. PMID: 7126180

Coniglio09: Coniglio M, Kreis W (2009). "Immobilization of flavonol 3-O-beta-heterodisaccharidase on porous glass and production of rutinose from rutin." Planta Med 75(13);1459-61. PMID: 19452439

Fiorucci06: Fiorucci S, Golebiowski J, Cabrol-Bass D, Antonczak S (2006). "Molecular simulations reveal a new entry site in quercetin 2,3-dioxygenase. A pathway for dioxygen?." Proteins 64(4);845-50. PMID: 16786599

Fiorucci07: Fiorucci S, Golebiowski J, Cabrol-Bass D, Antonczak S (2007). "Molecular simulations bring new insights into flavonoid/quercetinase interaction modes." Proteins 67(4);961-70. PMID: 17373707

Fittipaldi03: Fittipaldi M, Steiner RA, Matsushita M, Dijkstra BW, Groenen EJ, Huber M (2003). "Single-crystal EPR study at 95 GHz of the type 2 copper site of the inhibitor-bound quercetin 2,3-dioxygenase." Biophys J 85(6);4047-54. PMID: 14645093

HAYANO61: HAYANO S (1961). "[Hapticus of the anterior chamber lens]." Nihon Ganka Gakkai Zasshi 65;1921-3. PMID: 13905564

Hund99: Hund HK, Breuer J, Lingens F, Huttermann J, Kappl R, Fetzner S (1999). "Flavonol 2,4-dioxygenase from Aspergillus niger DSM 821, a type 2 CuII-containing glycoprotein." Eur J Biochem 263(3);871-8. PMID: 10469153

Karp04: Karp PD (2004). "Call for an enzyme genomics initiative." Genome Biol 5(8);401. PMID: 15287973

Kooter02: Kooter IM, Steiner RA, Dijkstra BW, van Noort PI, Egmond MR, Huber M (2002). "EPR characterization of the mononuclear Cu-containing Aspergillus japonicus quercetin 2,3-dioxygenase reveals dramatic changes upon anaerobic binding of substrates." Eur J Biochem 269(12);2971-9. PMID: 12071961

Krishnamurty70: Krishnamurty HG, Simpson FJ (1970). "Degradation of rutin by Aspergillus flavus. Studies with oxygen 18 on the action of a dioxygenase on quercetin." J Biol Chem 245(6);1467-71. PMID: 5442827

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lim02: Lim EK, Doucet CJ, Li Y, Elias L, Worrall D, Spencer SP, Ross J, Bowles DJ (2002). "The activity of Arabidopsis glycosyltransferases toward salicylic acid, 4-hydroxybenzoic acid, and other benzoates." J Biol Chem 277(1);586-92. PMID: 11641410

Oka71: Oka T, Simpson FJ, Child JJ, Mills C (1971). "Degradation of rutin by Aspergillus flavus. Purification of the dioxygenase, querecentinase." Can J Microbiol 17(1);111-8. PMID: 5555519

Oka71a: Oka T, Simpson FJ (1971). "Quercetinase, a dioxygenase containing copper." Biochem Biophys Res Commun 43(1);1-5. PMID: 5579942

Oka72: Oka T, Simpson FJ, Krishnamurty HG (1972). "Degradation of rutin by Aspergillus flavus. Studies on specificity, inhibition, and possible reaction mechanism of quercetinase." Can J Microbiol 18(4);493-508. PMID: 4623295

Oka72a: Oka T, Simpson FJ (1972). "Degradation of rutin by Aspergillus flavus. Quercetinase: isolation of a low molecular-weight form containing less carbohydrate." Can J Microbiol 18(7);1171-5. PMID: 4627146

Siegbahn04: Siegbahn PE (2004). "Hybrid DFT study of the mechanism of quercetin 2,3-dioxygenase." Inorg Chem 43(19);5944-53. PMID: 15360243

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


Report Errors or Provide Feedback
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 SRI International Pathway Tools version 18.5 on Thu Nov 27, 2014, BIOCYC14A.