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|
Expected Taxonomic Range: Fungi
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 22.214.171.124) (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]).
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
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
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
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
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
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
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
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
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
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
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
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
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