Abstract
The aim of this review is to give a general account on the oxidative microbial degradation of flavonols. Since now 50 years, various research groups have deciphered the way microorganisms aerobically deal with this important class of flavonoids. Flavonols such as rutin and quercetin are abundantly found in vegetal tissues and exudates, and it was thus patent that various microorganisms will bear the enzymatic machinery necessary to cope with these vegetal secondary metabolites. After initial studies focussed on the general metabolic capacity of various microorganisms towards flavonols, the so called rutin catabolic pathway was rapidly established in moulds. Enzymes of the path as well as substrates and products were known at the beginning of the seventies. Then during 30 years, only sporadic studies were focused on this pathway, before a new burst of interest at the beginning of the new century arose with structural, genomic and theorical studies mainly conducted towards quercetinase. This is the goal of this work to relate this 50 years journey at the crossroads of microbiology, biochemistry, genetic and chemistry. Some mention of the potential usefulness of the enzymes of the path as well as micro-organisms bearing the whole rutin catabolic pathway is also discussed.
Similar content being viewed by others
References
Adams M, Jia Z (2005) Structural and biochemical analysis reveal pirins to possess quercetinase activity. J Biol Chem 280:28675–28682
Agarwall G, Rajavel M, Gopal B, Srinivasan N (2009) Structure-based phylogeny as a diagnostic for functional characterization of proteins with a cupin fold. PLoS ONE 4:e5736
Antonczak S, Fiorucci S, Golebiowski J, Cabrol-Bass D (2009) Theorical investigations of the role played by quercetinase enzymes upon the flavonoids oxygenolysis mechanism. Phys Chem Chem Phys 11:1491–1501
Armand-Fraysse D, Lebreton P (1969) Recherches physiologiques sur les champignons III. Transformation métabolique de la rutine par les champignons lignivores. Bull Soc Chim Biol 51:563–578
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 35:131–141
Barz W (1971) Uber den abbau aromatisher verbindungen durch Fusarium oxysporum Schlecht. Arch Mikrobiol 78:341–352
Bowater L, Fairhurst SA, Just VJ, Bornemann S (2004) Bacillus subtilis YxaG is a novel Fe-containing quercetin 2,3-dioxygenase. FEBS Lett 557:45–48
Braune A, Gutschow M, Engst W, Blaut M (2001) Degradation of quercetin and luteolin by Eubacterium ramulus. Appl Environ Microbiol 62:5558–5567
Brown SB, Rajananda V, Holroyd JA, Evans EGV (1982) A study of the mechanism of quercetin oxygenation by 18O labelling. Biochem J 205:239–244
Child JJ, Simpson FJ, Westlake DWS (1963) Degradation of rutin by Aspergillus flavus. Factors affecting production of the enzyme system. Can J Microbiol 9:653–664
Child JJ, Oka T, Simpson FJ, Krishnamurty HG (1971) Purification and properties of a phenol carboxylic acid esterase from Aspergillus flavus. Can J Microbiol 17:1455–1463
Clissold PM, Ponting CP (2001) JmjC: cupin metalloenzyme-like domains in jumonji, hairless and phospholipase A2β. Trends Biochem Sci 26:7–9
Das S, Rosazza JPN (2006) Microbial and enzymatic transformations of flavonoids. J Nat Prod 69:499–508
Dunwell JM (1998) Cupins: a new superfamily of functionally-diverse proteins that include germins and plant seed storage proteins. Biotechnol Genet Eng 15:1–32
Dunwell JM, Gane PJ (1998) Microbial relatives of the seed storage proteins of higher plants: conservation of motifs in a functionally diverse superfamilly of enzymes. J Mol Evol 46:147–154
Dunwell JM, Khuri S, Gane PJ (2000) Microbial relatives of the seed storage proteins of higher plants: conservation of structure and diversification of function during evolution of the cupin superfamily. Microbiol Mol Biol Rev 64:153–179
Dunwell JM, Culham A, Carter CE, Sosa-Aguirre CR, Goodenough PW (2001) Evolution of functional diversity in the cupin superfamily. Trends Biochem Sci 26:740–746
Dunwell JM, Purvis A, Khuri S (2004) Cupins: the most functionally diverse protein superfamily? Phytochemistry 65:1–17
Fiorucci S, Golebiowski J, Cabrol-Bass D, Antonczak S (2004) Oxygenolysis of flavonoid compounds: DFT description of the mechanism for quercetin. ChemPhysChem 5:1726–1733
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 64:845–850
Fiorucci S, Golebiowski J, Cabrol-Bass D, Antonczak S (2007) Molecular simulations bring new insights into flavonoid/quercetinase interaction mode. Proteins 67:961–970
Fittipaldi M, Steiner RA, Matsushita M, Dijkstra BW, Groenen EJJ, Huber M (2003) Single-crystal EPR study at 95 Hz of the type 2 copper site of the inhibitor-bound quercetin 2,3-dioxygenase. Biophys J 85:4047–4054
Fusetti F, Schröter 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 10:259–268
Gallego MV, Pinaga F, Ramon D, Valles S (2001) Purification and characterization of an α-L-rhamnosidase from Aspergillus terreus of interest in wine making. J Food Sci 65:204–209
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 44:193–201
Haluk JP, Metche M (1970) Transformation microbiologique de la quercetine par Aspergillus niger Van Tieghem. Bull Soc Chim Biol 52:667–676
Hattori S, Noguchi I (1959) Microbial degradation of rutin. Nature 184:1145–1146
Hay GW, Westlake DWS, Simpson FJ (1961) Microbial decomposition of rutin. Can J Microbiol 7:921–931
Hirooka K, Kunikane S, Matsuoka H, Yoshida K-I, Kunamoto K, Tojo S, Fujita Y (2007) Dual regulation of the Bacillus subtilis regulon comprising the lmrAB and yxaGH operons and yxaF gene by two transcriptional repressors, LmrA and YxaF, in response to flavonoids. J Bacteriol 189:5170–5182
Hund H-K, Breuer J, Lingans F, Hüttermann J, Kappel R, Fetzner S (1999) Flavonol 2,4-dioxygenase from Aspergillus niger DSM 821, a type 2 CuII-containing glycoprotein. Eur J Biochem 263:871–878
Iacazio G (2005) Increased quercetinase production by Penicillium olsonii using fractional factorial design. Process Biochem 40:379–384
Kaizer J, Balogh-Hergovich E, Czaun M, Csay T, Speier G (2006) Redox and non-redox metal assisted model systems with relevance to flavonol and 3-hydroxyquinolin-4(1H)-one 2,4-dioxygenase. Coord Chem Rev 250:2222–2233
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 269:2971–2979
Krishnamachari V, Levine LH, Paré PW (2002) Flavonoid oxidation by the radical generator AIBN: a unified mechanism for quercetin radical scavenging. J Agric Food Chem 50:4357–4363
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 245:1467–1471
Kurosawa Y, Ikeda K, Igami F (1973) Alpha-L-rhamnosidase of the liver of Turbo cornutus and Aspergillus niger. J Biochem 73:31–37
Mamma D, Kalogeris E, Hatzinikolaou DG, Lekanidou A, Kekos D, Macris BJ, Christakopoulos P (2004) Biochemical characterization of the multi-enzyme system produced by Penicillium decumbens grown on rutin. Food Biotechnol 18:1–18
Manzanares P, de Graaf LH, Visser J (1997) Purification and characterization of an a-L-rhamnosidase from Aspergillus niger. FEMS Microbiol Lett 157:279–283
Manzanares P, Orejas M, Ibanez E, Valles S, Ramon D (2000) Purification and characterization of an α-L-rhamnosidase from Aspergillus nidulans. Lett Appl Microbiol 31:198–202
Manzanares P, van den Broeck HC, de Graaf LH, Visser J (2001) Purification and characterization of two different α-L-rhamnosidases, RhaA and RhaB, from Aspergillus aculeatus. Appl Environ Microbiol 67:2230–2234
Medina ML, Kiernan VA, Francisco WA (2004) Proteomic analysis of rutin-induced secreted proteins from Aspergillus flavus. Fungal Genet Biol 41:327–335
Medina ML, Haynes PA, Breci L, Francisco WA (2005) Analysis of secreted proteins from Aspergillus flavus. Proteomics 5:3153–3161
Merkens H, Fetzner S (2008) Transcriptional analysis of the queD gene coding for quercetinase of Streptomyces sp. FLA. FEMS Microbiol Lett 287:100–107
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 187:475–487
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 47:12185–12196
Mills ENC, Jenkins J, Marigheto N, Belton PS, Gunning AP, Morris VJ (2002) Allergens of the cupin superfamily. Biochem Soc Trans 30:925–929
Monti D, Pisvejcova A, Kren V, Lama M, Riva S (2004) Generation of an a-L-rhamnosidases library and its application for the selective derhamnosylation of natural products. Biotechnol Bioeng 87:763–771
Narikawa T, Karaki Y, Shinoyama H, Fujii T (1998) Rutin degradation by culture filtrates from Penicillia. Nippon Nogeik Kaishi 72:473–479
Narikawa T, Shinoyama H, Fujii T (2000) A β-rutinosidase from Penicillium rugulosum IFO 7242 that is a peculiar flavonoid glycosidase. Biosci Biotechnol Biochem 64:1317–1319
Neznanov N, Kondratova A, Chumakov KM, Neznanova L, Kondratov R, Banerjee AK, Gudkov AV (2008) Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin. DNA Cell Biol 27:191–198
Noguchi I (1963) The degradation of flavonols by Pullularia fermentans var. candida. Bot Mag Tokyo 76:191–198
Oka T, Simpson FJ (1971) Quercetinase: a dioxygenase containing copper. Biochem Biophys Res Commun 43:1–5
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 18:1171–1175
Oka T, Simpson FJ, Child JJ, Mills SC (1971) Degradation of rutin by Aspergillus flavus. Purification of the dioxygenase, quercetinase. Can J Microbiol 17:111–118
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 18:493–508
Omori T, Shiozawa K, Sekiya M, Minoda Y (1986) Formation of 2,4,6-trihydroxy-carboxylic acid and 2-protocatechuoylphloroglucinol carboxylic acid from rutin by bacteria. Agric Biol Chem Tokyo 50:779–780
Padrn J, Grist KL, Clark JB, Wender SH (1960) Specificity studies on an extracellular enzyme preparation obtained from quercetin grown cells of Aspergillus. Biochem Biophys Res Commun 3:412–416
Pang H, Bartlam M, Zeng Q, Miyatake H, Hisano T, Miki K, Wong L, Gao GF, Rao Z (2004) Crystal structure of human pirin. J Biol Chem 279:1491–1498
Pietta P-G (2000) Flavonoids as antioxidants. J Nat Prod 63:1035–1042
Pillai BVS, Swarup S (2002) Elucidation of the flavonoid catabolism pathway in Pseudomonas putida PML2 by comparative metabolic profiling. Appl Environ Microbiol 68:143–151
Puti M, Kalra S (2005) Purification and characterization of naringinase from a newly isolated strain of Aspergillus niger 1344 for the transformation of flavonoids. World J Microbiol Biotechnol 21:753–758
Rajavel M, Kulkarni NN, Gopal B (2008) Conformational studies suggest that the double stranded β helix scaffold provides an optimal balance between protein stability and function. Protein Pept Lett 15:244–249
Rao JR, Cooper JE (1994) Rhizobia catabolize nod gene-inducing flavonoids via C-ring fission mechanisms. J Bacteriol 176:5409–5413
Rao KV, Weisner NT (1981) Microbial transformation of quercetin by Bacillus cereus. Appl Environ Microbiol 42:450–452
Rao JR, Sharma ND, Hamilton JTG, Boyd DR, Cooper JE (1991) Biotransformation of the pentahydroxy flavone quercetin by Rhizobium loti and Bradyrhizobium stains (Lotus). Appl Environ Microbiol 57:1563–1565
Rose K, Fetzner S (2006) Identification of linear plasmid pAM1 in the flavonoid degrading strain Actinoplanes missouriensi T (DSM 43046). Plasmid 55:249–254
Schaab MR, Barney BM, Francisco WA (2006) Kinetic and spectroscopic studies on the quercetin 2,3-dioxygenase from Bacillus subtilis. Biochemistry 45:1009–1016
Schneider H, Blaut M (2000) Anaerobic degradation of flavonoids by Eubacterium ramulus. Arch Microbiol 173:71–75
Schoefer L, Mohan R, Schwiertz A, Braune A, Blaut M (2003) Anaerobic degradation of flavonoids by Clostridium orbiscindens. Appl Environ Microbiol 69:5849–5854
Siegbahn PEM (2004) Hybrid DFT study of the mechanism of quercetin 2,3-dioxygenase. Inorg Chem 43:5944–5953
Simpson FJ, Talbot G, Westlake DWS (1960) Production of carbon monoxide in the enzymatic degradation of rutin. Biochem Biophys Res Commun 2:15–18
Simpson FJ, Narasimhachari N, Westlake DWS (1963) Degradation of rutin by Aspergillus flavus. The carbon monoxide producing system. Can J Microbiol 9:15–25
Steiner RA, Kalk KH, Dijkstra BW (2002a) Anaerobic enzyme substrate structures provide insight into the reaction mechanism of the copper-dependent quercetin 2,3-dioxygenase. Proc Natl Acad Sci USA 99:16625–16630
Steiner RA, Kooter IM, Dijkstra BW (2002b) Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 1. Ligand-induced coordination changes probed by X-ray crystallography: inhibition, ordering effect, and mechanistic insights. Biochemistry 41:7955–7962
Steiner RA, Meyer-Klaucke W, Dijkstra BW (2002c) Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 2. X-ray absorption studies of native enzyme and anaerobic complexes with the substrates quercetin and myricetin. Biochemistry 41:7963–7968
Tranchimand S, Tron T, Gaudin C, Iacazio G (2005) Evaluation of phenolics and sugars as inducers of quercetinase activity in Penicillium olsonii. FEMS Microbiol Lett 253:289–294
Tranchimand S, Tron T, Gaudin C, Iacazio G (2006) First chemical synthesis of three natural depsides involved in flavonoid catabolism and related to quercetinase catalysis. Synth Commun 36:587–597
Tranchimand S, Ertel G, Gaydou V, Gaudin C, Tron T, Iacazio G (2008) Biochemical and molecular characterization of a quercetinase from Penicillium olsonii. Biochimie 90:781–789
van den Bosch M, Swart M, van Gunsteren WN, Canters GW (2004) Simulation of the substrate cavity dynamics of quercetinase. J Mol Biol 344:725–738
van der Heiden M, Nondmann DH, van der Helm MJ, Verrips CT, Swarthoff T, Smits A (1998) WO1997EP07138 19971210
Westlake DWS (1963) Microbial degradation of quercitrin. Can J Microbiol 9:211–220
Westlake DWS, Simpson FJ (1961) Degradation of rutin by Aspergillus flavus. Factors affecting production of the enzyme system. Can J Microbiol 7:33–44
Westlake DWS, Spencer JFT (1966) The utilisation of flavonoid compounds by yeast and yeast like fungi. Can J Microbiol 12:165–174
Westlake DWS, Talbot G, Blakley ER, Simpson FJ (1959) Microbial decomposition of rutin. Can J Microbiol 5:621–629
Westlake DWS, Roxburgh JM, Talbot G (1961) Microbial production of carbon monoxide from flavonoids. Nature 189:510–511
Winter J, Moore LH, Dowell VR Jr, Bokkenheuser VD (1989) C-ring cleavage of flavonoids by human intestinal bacteria. Appl Environ Microbiol 55:1203–1208
Yoshida K-I, Ohki Y-H, Murata M, Kinehara M, Matsuoka H, Satomura T, Ohki R, Kumano M, Yamane K, Kunamoto K, Fujita Y (2004) Bacillus subtilis LmrA is a repressor of the lmrAB and yxaGH operons: identification of its binding site and functional analysis of lmrB and yxaGH. J Bacteriol 186:5640–5648
Acknowledgments
This work was supported in part by a grant (no. 10659) from the “Ministère Délégué à l’Enseignement Supérieur et à la Recherche” to Sylvain Tranchimand.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tranchimand, S., Brouant, P. & Iacazio, G. The rutin catabolic pathway with special emphasis on quercetinase. Biodegradation 21, 833–859 (2010). https://doi.org/10.1007/s10532-010-9359-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10532-010-9359-7