Table 1. Redox potentials of various laccases and corresponding sequence alignments. The conserved HCH tripeptide, axial ligand (last) are marked in bold. N.d refers to laccases whose sequence was not determined. The pair of aminoacids marked in bold and italics is involved in the Piontek hypothesis (see text). Unless stated (UP – uniprot database, PDB – Protein Data Bank), the sequence codes are from GenBank. E⁰ is measured vs. NHE......................... 14

Table 2. Recent cultivation conditions and purification procedures with their yield and fold factors for several laccase purifications from different organisms.............................................. 29

Table 3. Statistical data of K_m and k_cat values for most used laccase substrates...................... 30

Table 4. Some characterization data regarding some recently purified laccases. The references for each organism can be found in Table 2......................................................................... 31

Table 5. Effects of various potential laccase inducers upon the laccase activity in S. sclerotiorum................................................................................................................................... 49

Table 6. Biomass and laccase activity variations when different carbon and nitrogen sources were used............................................................................................................................ 50

Table 7. Concentration/purification of laccase using salt precipitation and chromatographic methods...................................................................................................................... 68

Table 8. Substrate catalytic parameters of the purified laccase obtained by non-linear fitting model using Origin 8............................................................................................................. 74

Table 9. Michaels-Menten parameters for three substrates for five forms of the purified laccase obtained by Eadie–Hofstee linearization in case of biphasic cases (Q₀H₂) and non-linear fitting using GraphPad for normal curves................................................................................ 93

Table 10. Prooxidant, antioxidant, enzymatic kinetic parameters and redox potentials of the studied compounds................................................................................................................ 108

Table 11. Floral, geographical origins and description of the studied propolis samples......... 119

Table 12. Correlation coefficients between several calculated parameters of the kinetic profile of DPPH bleaching assays and some relevant IR and UV-vis absorbances......................... 121

Table 13. Distinct bands in FT-IR spectra found in propolis extracts................................... 122

Table 14. Geographical origins and their numbering the propolis samples taken into this section study (interaction with hemoglobin)........................................................................... 125

Table 15. Correlation coefficients between various antioxidant measurement methods. “DPPH” denotes the percent decrease in DPPH absorbance in 680 seconds. GAE denotes the gallic acid equivalents, in mg/mL. HAPX denotes the ratio between rates of ascorbate consumption by hemoglobin and peroxide in the absence and presence of propolis, respectively. EPR denotes the area under the EPR signal; as determined by double integration. Details are found in Materials and Methods............................................................................................... 130

Table 16. Several parameters regarding binary mixture experiments................................... 133

Abbreviations

Å – ångström (1Å=10^-10 m);

ABTS – a well known laccase substrate: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid);

ANOVA – analysis of variance;

APCI – atmospheric-pressure chemical ionization;

AUC – area under the curve;

C/N – carbon to nitrogen ratio;

cAMP – cyclic adenosine monophosphate;

CAT – catalase;

CD – circular dichroism;

CER – ceruloplasmin;

CotA – the protein (with laccase activity) encoded by the gene with the same name involved in spor coat dvelopement of Bacillus subtilis;

CueO – copper efflux oxidase (the laccase from Escherichia coli);

CuTPP – [5, 10, 15, 20-tetrakis(N-methylpyridyl-4)porhinato]copper(II) tetratosylate);

2,6-DMP – 2,6-dimethoxyphenol;

D_4h – denotes a symmetry group;

Da – daltons;

DAD – diode array detector;

DMPO – 5,5-dimethyl-pyrroline N-oxide;

DPPH – 2,2-diphenyl-1-picrylhydrazyl;

DTT – dithyotreitol;

E^○ – normal electrode potential;

EPR – electron paramagnetic resonance;

ESI – electrospray ionization;

FPLC – fast protein liquid chromatography;

(FT)IR – Fourier transformed infrared;

GAE – gallic acid equivalent;

GuHCl – guanidine hydrochloride;

HAPX – hemoglobin-ascorbate peroxidase;

Hb – hemoglobin;

HOMO – highest occupied molecular orbital;

k_cat – catalytic constant (turnover number);

K_m – Michaelis-Menten constant;

LAC – three domain laccase (common laccase);

LC(-MS) – liquid chromatography (-mass spectrometry);

LMCT – ligand to metal charge transfer;

LUMO – lowest unoccupied molecular orbital;

MES – 2-(N-morpholino)ethanesulfonic acid used as buffer;

MOPS – 3-(N-morpholino)propanesulfonic acid used as buffer;

NHE – normal hydrogen electrode;

nm – nanometer;

NMR – nuclear magnetic resonance;

NR – nitrite reductase;

p – the probability of obtaining a statistic test;

PAGE – polyacrylamide gel electrophoresis;

PBS – phosphate buffer saline;

PCA –Principal Component Analysis;

PDB – protein data bank;

Ph-OH – generic formula for phenolic compound;

pQF – prooxidant quercetin factor;

Q₀ – dimethoxy-5-methyl-p-benzoquinone;

QF – quercetin factor;

QM/MM – quantum mechanical and molecular mechanics;

RGB – red green blue color channel;

RNS – reactive nitrogen species;

ROS – reactive oxygen species;

RP – reversed phase;

rpm – rotations per minute;

RSD – relative standard deviation;

SD – standard deviation;

SDS – sodium dodecyl sulfate;

SLAC – small laccase (one domain laccase);

SOD –superoxide dismutase;

T1Cu – type 1 copper;

T2Cu – type 2 copper;

T3Cu – type 3 copper;

TAPS – 3-[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]amino]propane-1-sulfonic acid used as buffer;

TEAC – trolox equivalent antioxidant capacity;

TMB – tetramethylbenzidine;

TRIS – 2-amino-2-hydroxymethyl-propane-1,3-diol used as buffer;

U – enzymatic unit;

UV-vis – ultra violet and visible;

V – volt;

WE –working electrode;

Acknowledgements

I want to give thanks to prof. dr. Florin Dan Irimie for allowing me to be his PhD student and for all his time afforded whenever it was required. I am very gratefully to conf. dr. Radu Silaghi-Dumitrescu who was a wonderful scientific supervisor, for all his impartial and kind help, advice and scientific guidance offered from his nice and respectful conviction. Many thanks are also given to Dr. Dirk Heering for all his scientific advice, nice time spent together and for allowing me to work in his laboratory. Prof. dr. Grigore Damian, conf. dr. Marcel Parvu, conf. dr. Costel Sarbu, dr. Iulia Lupan, dr. Alex Lupan, dr. Zsuzsa Darula, Cristina Coman are all thanked for their help and helpful discussions during the work of this thesis.

In the end I want to mention that I will remain with wonderful memories from laboratory 6 wherever I will be in future, thus all people met there are nicely hugged.

Aims of the thesis

The present thesis has five main objectives which were stated in a preliminary form before the work was started and suffered several adjustments during the work proceeded. Each of these objectives contains several main steps which were foreseen in the research thesis project or was established during the ongoing procedures.

Determination of optimum conditions considering maximum laccase activity in liquid culture of Sclerotinia sclerotiorum

Evaluation of several types of liquid mediums upon laccase secretion;
Assessing the influence of numerous important parameters/conditions upon laccase production by the fungus such as: pH, N and C sources, time, several inducers;
Evaluation of some important physiologic relevant factors upon laccase regulation in order to bring some insights of its physiologic role;

Isolation, purification and characterization of Sclerotinia sclerotiorum laccase

· Establishment of suitable protocols for laccase isolation and purification using chromatographic and electrophoretic facilities;

· Determination of specific activity and biochemical properties (K_M, k_cat, optimum pH and temperature, thermostability, substrate selectivity) of the purified enzyme;

· Spectral characterization of the purified enzyme (UV-vis, CD, EPR, MS);

Elucidation of the mechanism of the reactions catalyzed by the pure enzyme

· Characterization of possible reaction intermediates and their kinetics;

· Study of enzyme – substrate interaction;

Applications of the Sclerotinia sclerotiorum laccase

· Establishment of protocols suitable for evaluations of prooxidant and antioxidant activities of polyphenols and some natural extracts;

Theoretical and experimental studies of model compounds for laccases

· Evaluation of reactivity towards some ligands and laccase substrates of some copper complexes;

· Theoretical studies of laccase copper centers concerning their reactivity and spectral behaviour.

General Introduction

roteins having one or more copper ions as cofactors play very important roles in cellular metabolism of all living organisms. They are involved in photosynthesis, oxidative phosphorylation, homeostasis of metal ions and catabolism of many nutrients. The main reactions involving copper proteins are electron transfer, this due to copper ability to exist in two oxidation states Cu⁺ and Cu²⁺. Copper centers in proteins have such a coordination sphere provided by the polypeptidic structure so that the transition from one oxidation state to another to be thermodynamically favorable.

The simplest copper dependent proteins are azurins and plastocyanines, they are usually involved in electron transfer reactions. Other more complex proteins, with copper ions in the active sites, such as galactose oxidase, nitrite reductase, ceruloplasmin, ascorbate reductase, bilirubin oxidase and last but not least laccase, are involved electron transfer reactions from reduced substrates to electron deficient molecules.

Laccase (p-diphenols: dioxigen oxidoreductase) is an oxidoreductase (EC 1.10.3.2) with four copper ions in two active sites, which catalyzes the oxidation of reduced substrates usually phenols or aromatic amines, coupled with the reduction of molecular oxygen to water. Laccase is one of the oldest enzymes ever studied, it was described for the first time by Yoshida (1883) and categorized by Bertrand (1895) as a copper containing oxidase. However, only in recent decades, when it was discovered that laccases are part of the enzymatic arsenal involved in wood degradation by white rot fungi, study of these enzymes has greatly increased. A more recent interest in this enzyme is its involvement in the virulence of some phytopathogenic fungi, as is the case of the present thesis.

Currently, this enzyme is the central subject of many worldwide research groups, due to scientific curiosity and its high potential in numerous applications in biotechnology and bioanalytical chemistry.

Summary of the content of the thesis

The first chapter describes the most recent research on the overall structural features of laccases as well as on the structures and properties of the active sites, along with the currently proposed mechanisms of reaction. Laccase (p-diphenol:dioxygen oxidoreductase), one of the oldest discovered enzymes, contains four copper ions in two active sites and catalyzes a monoelectronic oxidation of substrates such as phenols and their derivatives, or aromatic amines, coupled to a four-electron reduction of dioxygen to water. The catalytic mechanism was studied for decades but is still not completely elucidated, especially in terms of the reduction of dioxygen to water. The key structural features of this enzyme are under research in several groups using techniques such as X-ray diffraction, electron paramagnetic resonance (EPR) spectroscopy, site-directed mutagenesis. The high interest in laccases is explained by the large number of biotechnological applications. Their distribution in nature, the physiologic role, most used methods for purification and biochemical properties and parameters used for their characterization are also described. Numerous applications of laccases such as textile industry, wood processing paper production, pharmaceutical and chemical industries and others are described. Some biological aspects regarding Sclerotinia sclerotiorum phytopathogenic fungus and reasons for using this organism as laccase source are presented at the end of the chapter. In the last part of the chapter some copper complexes used as models for laccase active sites are discussed.

The second chapter describes the factors affecting the production of laccase from the phytopathogenic fungus Sclerotinia sclerotiorum (Lib.) de Bary. The carbon/nitrogen ratio appears to be of great importance. Rather than a simple nutrient-rich nitrogen source, yeast extract behaves as a true laccase upregulator, apparently acting via a stress pathway. Chelidonium majus extract, a known antifungal agent, acts in a similar manner. The compound(s) in the yeast extract responsible for enhancing laccase synthesis are suggested to be hydrolysable small organic molecules. Both extracts reduce biomass and sclerotia development and enhance laccase production, leading to an increase in laccase activity by one order of magnitude compared to controls. The pH of the medium, a well-known virulence regulator for this fungus, also acts as a true laccase regulator, though via a different mechanism. The effect of pH appeared to be linked to the acidification kinetics of the extracellular medium during fungal development. A number of other known laccase inducers were found to enhance laccase production at most two-fold.

Chapter three contains information regarding the production, purification and characterization of a laccase from the phytophathogenic fungus Sclerotinia sclerotiorum. This laccase is identified by mass spectrometry with a sequence coverage of 74.9% (458/577 AA) revealing that the protein is identical or highly homologous to a predicted oxidoreductase from this species (A7EM18 in the Uniprot database); the closest homologous protein previously isolated from a fungus is the Melanocarpus albomyces, with only 35% identity. The UV-vis spectral features of this laccase classify it as a “yellow” one. The EPR spectrum nevertheless demonstrates resemblance to blue laccases – including the type 1 center not detectable in UV-vis spectra. The presence of type 3 coppers was proven by fluorescence spectrum and by 330 nm band in UV-vis. The purified laccase has an apparent molecular mass of 70 kDa and appears as a monomer. The values of K_M and k_cat were determined for ABTS, 2,6-dimethoxyphenol, p-phenylenediamine and guaicol and are typical of a laccase. The optimal pH value is around 4 except for ABTS, for which activity is linearly increasing with acidity. The high laccase activity in liquid culture makes Sclerotinia sclerotiorum a useful source of laccase for practical applications.

In chapter four it is provided the first evidence that the yellow laccase isolated from Sclerotinia sclerotiorum is obtained from a blue form by covalent, but nevertheless reversible modification with a polyphenolic product. Yellow laccases lack the typical blue type 1 Cu absorption band around 600 nm, but are nevertheless multicopper oxidases with laccase properties. After separating the polyphenols, a typical blue laccase is obtained. With ABTS as model substrate for this blue enzyme, a purple adduct is formed with a spectrum nearly identical to that of the 1:1 adduct of an ABTS radical and Tyr. This modification significantly increases the stability and substrate affinity of the enzyme, not by acting primarily as bound mediator, but by allosteric activation that also alters the type 1 Cu site. Thus, S. sclerotiorum yellow laccase is an intrinsically blue multi-copper oxidase that autocatalytically activates itself upon first encounter with a radical-forming aromatic substrate.

The fifth chapter contains numerous results regarding the application of the purified enzyme on antioxidant and prooxidant properties of some phenolics and propolis extracts. A transient species may be detected with UV-vis and EPR spectroscopy during turnover of a laccase with quercetin; this species is assigned as a quercetin-derived radical, based on EPR spectra as well as based on UV-vis similarities with previously reported data on a quercetyl radical obtained via a non-enzymatic route. The formation and decay of this species correlate well with the prooxidant reactivity manifested by flavonoids in the presence of laccase. An assay for the prooxidant reactivity of natural compounds is proposed based on the results reported here; this assay has the advantages of using a biologically-relevant process (hemoglobin oxidation), and of not needing added oxidizing agents such as peroxide or superoxide. Correlations, or the lack thereof, between the prooxidant parameters and the redox potentials, antioxidant capacities and lipophilicities, are analyzed. New assays for antioxidant activity of natural extracts are also described. It can be noted that the laccase employed in this study does display structural and reactivity-related similarities to a range of other proteins, which includes ceruloplasmin.

The last chapter of the thesis contains the results regarding molecular modelling of laccase active sites and the experiments describing the reactivity of some copper complexes used as models for type 2 copper sites. Laccases contain a blue mononuclear copper center known as ‘type-1’, and thought to be the primary electron acceptor from organic substrates during the catalytic cycle. A small group of laccases are also known that lack the 600 nm band and hence the blue color (“yellow laccases”). In first section it is reported the use of semiempirical (ZINDO/S-CI) calculations in order to simulate UV-vis spectral parameters for the laccase type 1 copper, attempting to assign geometrical and electronic structure elements that may control the color of this site. The ~600-nm band of the type 1 copper is confirmed to arise mainly from sulfur-to-copper charge transfer, and strong distortions allowing for its displacement by more than 200 nm and/or its dissolution are identified. In the second section some copper porphyrinates are analysed with respect to its reactivity towards some laccase substrate and some other redox active compounds. Copper porphyrinates are generally known to display a less diverse reactivity compared to their iron counterparts. It is examined a water-soluble copper porphyrinate for its ability to engage in reactions involving axial ligation to the copper or possible redox cycling. Although UV–vis spectra indicate an expected lack of reactivity, electron paramagnetic resonance spectra (EPR) reveal an unexpected wealth of changes in electronic structures at the copper, induced by potential ligands such as imidazole or nitrite, but also by seemingly unexpected candidates for ligands, such as 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and guaiacol, as well as by dithionite. An important function of many copper-containing proteins is activation of O₂ and subsequent substrate oxidation. The Cu (III) oxidation state is generally considered to be less accessible because of the highly positive Cu (III)/Cu (II) redox potentials with typical amino acid ligands. In the last part it is employed density functional (DFT) calculations to explore to what extent copper (III) may be accessed in a biologically-relevant coordination environment around a mononuclear copper center, by breaking the oxygen-oxygen bond in a copper-(hydro) peroxide complex. In agreement with previous findings on copper models with related coordination patterns, the formally high-valent copper complex produced by O-O bond cleavage appears to in fact harbor both oxidizing equivalents on the ligands. The potential energy surface for such a reaction reveals that with the three-histidine binding motif at the copper, O-O bond cleavage is not impossible, but rather disfavored thermodynamically.

General conclusions

· Optimal conditions under which the S. sclerotiorum laccase can be produced were determined. The carbon and nitrogen sources and C/N ratio appear to be of great importance for laccase production in this fungus. Rather than a simple nutrient-rich nitrogen source, yeast extract behaves as a true laccase inducer/upregulator, apparently acting via a stress pathway. Chelidonium majus extract, a known antifungal agent, acts in a similar manner. The pH of the medium, a well-known virulence regulator for this fungus, also acts as a true laccase regulator, though via a different mechanism. The effect of pH appears to be linked to the acidification kinetics of the extracellular medium during fungal development. Thus, evidence is shown that this enzyme is involved in stress response pathways, most likely connected to virulence.

· Sclerotinia sclerotiorum laccase has been isolated, and its catalytic properties characterized. Notably, although this laccase can be classified as a “yellow laccase” based on the UV-vis spectrum, the “blue” T1 center is nevertheless observable in the EPR spectrum. The extent to which the S. sclerotiorum laccase may indeed allow definition of a new type of laccase (neither truly “blue”, nor truly “yellow”) remains to be explored, especially as for most yellow laccases the EPR spectra have not been reported; should such a class be confirmed, a term such as “mixed blue-yellow” might be appropriate.

· Direct evidence for an example where a blue laccase can be converted to a yellow form in vitro by covalent modification at the T1 site, with metabolites produced by the laccase itself was provided. Moreover, this autocatalytic modification significantly improves the structural and catalytic properties of the enzyme. In essence, S. sclerotiorum yellow laccase is an intrinsically blue multi-copper oxidase that has activated itself upon first encounter with a polyphenolic substrate. A tyrosine residue was identified near the T1 site, which may be the target of such modifications.

· A transient species may be detected with UV-vis and EPR spectroscopy during turnover of a laccase with quercetin; this species is assigned as a quercetin-derived radical, based on EPR spectra as well as based on similarities with previously reported data. Furthermore, this species correlates well with the prooxidant reactivity manifested by flavonoids in the presence of laccase. An assay for prooxidant reactivity of natural compounds is proposed based on these results, which has the advantages of using a biologically-relevant process (hemoglobin oxidation), and of not needing added oxidizing agents such as peroxide or superoxide. Correlations, or the lack thereof, between the parameters obtained from this assay and redox potentials, antioxidant capacities and lipophilicities, are discussed. It was also noted that the laccase employed in this study does display structural and reactivity-related similarities to a range of other proteins, which includes the serum ceruloplasmin, and also displays reactivity similarities with heme-containing peroxidases. In addition, a new more informative and effective scale of antioxidant capacity is obtained by applying PCA on DPPH (2, 2-diphenyl-1-picrylhydrazyl) bleaching kinetic profiles. In order to obtain comparable antioxidant activities, a non-dimensional parameter was generated which is termed the quercetin factor (QF), which defines the ratio between quercetin equivalent in mg/L of the assayed propolis sample and the corresponding propolis concentration in mg/L. Further application of this methodology to other botanical extracts will confirm this new method for assessing antioxidant activity.

· The coordinative chemistry of copper porphyrinates may be distinctly more complex than previously described, and that EPR but not UV-vis spectroscopy is the method of choice for investigating this new chemistry.

· Using computational methods, torsion and elongation-type deformations have been identified, which allow a “blue” tri-coordinated type 1 copper center to apparently lose its characteristic 600-nm band responsible for its blue color both by shifting it by more than 200 nm, and, in some cases, by decreasing the extinction coefficients. However, DFT calculations suggest that such distortions might also be detectable with EPR spectroscopy.

· Unlike in related iron or manganese complexes, high-valent states appear not to be achievable via peroxo chemistry in copper complexes – even though O-O bond cleavage per se appears to entail reasonably low energy barriers; this may be interpreted to be due to a difference in redox potentials, which makes the peroxide-derived hydroxo and oxo ligands easier to oxidize than Cu (II).

References

1) Abdullah J., Ahmad M., Heng L.Y., Karuppiah N., Sidek H., An optical biosensor based on immobilization of laccase and MBTH in stacked films for the detection of catechol, Sensors 7 (2007) 2238-2250;

2) Aboelella N.W., Gherman B.F., Hill L.M.R., York J.T., Holm N., Young Jr. V.G., Cramer C.J., Tolman W.B., Effects of thioether substituents on the O₂ reactivity of β-Diketiminate−Cu(I) complexes: probing the role of the methionine ligand in copper monooxygenases, J. Am. Chem. Soc. 128 (2006) 3445-3458;

3) Aboelella N.W., Kryatov S.V., Gherman B.F., Brennessel W.W., Young Jr. V.G., Sarangi R., Rybak-Akimova E.V., Hodgson K.O., Hedman B., Solomon E.I., Cramer C.J., Tolman W.B., Dioxygen activation at a single copper site: structure, bonding, and mechanism of formation of 1:1 Cu−O₂ adducts, J. Am. Chem. Soc. 126 (2004) 16896-16911

4) Adlercreutz H., Mazur W., Phyto-oestrogens and Western diseases, Ann. Med. 29 (1997) 95–120;

5) Adman E.T., Copper protein structures, Adv. Protein. Chem. 42 (1991) 144-197;

6) Agrios GN., Plant Pathology 5^th ed., Elsevier, Academic Press, San-Diego, CA, (2006). p. 546-550;

7) Akerstrom B., Maghzal G.J., Winterbourn C.C., Kettle A.J., The lipocalin α1-microglobulin has radical scavenging activity, J. Biol. Chem. 282 (2007) 31493–31503;

8) Andberg M., Hakulinen N., Auer S., Saloheimo M., Koivula A., Rouvinen J., Kruus K., Essential role of the C-terminus in Melanocarpus albomyces laccase for enzyme production, catalytic properties and structure, FEBS J. 276 (2009) 6285–6300;

9) Andersen S.O., Insect cuticular sclerotization: A review, Insect Biochem. Mol. Biol. 40 (2010) 166-178;

10) Antonini E., Brunori M., Hemoglobin and myoglobin in their reaction with ligands: North-Holland, Amsterdam, The Neatherlands, (1971) pp. 153

11) Apak R., Guclu K., Demirata B., Ozyurek M., Celik S.E., Bektasoglu B., Berker K. I., Özyurt, D., Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay, Molecules 12 (2007) 1496-1547;

12) Ardon O., Kerem Z., Hadar Y., Enhancement of laccase activity in liquid cultures of the ligninolytic fungus Pleurotus ostreatus by cotton stalk extract, J. Biotechnol. 51 (1996) 201-207;

13) Arora D.S., Rampal P., Laccase production by some Phlebia species. J. Basic Microbiol. 42 (2002) 295-301;

14) Aruoma O.I., Assessment of potential prooxidant and antioxidant actions, JAOCS 73 (1996) 1617-1625;

15) Ashworth P., Dixon W.T., Secondary radicals in the autoxidation of hydroquinones and quinones, J. Chem. Soc. D 9 (1972) 1130-1133;

16) Augustine A.J., Kjaergaard C., Qayyum M., Ziegler L., Kosman D.J., Hodgson K.O., Hedman B., Solomon E.I., Systematic perturbation of the trinuclear copper cluster in the multicopper oxidases: the role of active site asymmetry in itsrReduction of O₂ to H₂O, J. Am. Chem. Soc. 132 (2010) 6057–6067;

17) Aust S.D., Swaner P.R., Stahl J.D., Detoxification and metabolism of chemicals by white-rot fungi. Pesticide decontamination and detoxification, Oxford University Press, Washington, D.C., (2003) pp. 3;

18) Averill B., Eldredge P., General Chemistry: principles, patterns, and applications, Prentice Hall, (2006) Chapter 23;

19) Ayse K., Beraat O., Samim S., Review of methods to determine antioxidant capacities, Food Anal. Methods 2 (2009) 41-60;

20) Baldrian P., Fungal laccases – occurrence and properties, FEMS Microbiol. Rev. 30 (2006) 215–242;

21) Bankova V.S., Popov S.S., Marekov N.I., A study on flavonoids of propolis, J. Nat. Prod. 46 (1983) 471-474;

22) Bankova V.S., Chemical diversity of propolis and the problem of standardization, J. Ethnopharmacol. 100 (2005a) 114–117;

23) Bankova V.S., Recent trends and important developments in propolis research, Evid. base Compl. Alternative Med. 2 (2005b) 29-32;

24) Banskota A.H., Tezuka Y., Adnyana I.K., Ishii E., Midorikawa K., Matsushige K., Kadota S. Hepatoprotective and anti Helicobacter pylori activities of constituents from Brazilian propolis, Phytomedicine, 8 (2001) 16–23;

25) Bar-Nun N., Lev A.T., Harel E., Mayer A.M., Repression of laccase formation in Botrytis cinerea and its possible relation to phytopathogenicity, Phytochemistry 27 (1988) 2505–2509;

26) Barreca A.M., Fabbrini M., Galli C., Gentili P., Ljunggren S., Laccase/mediated oxidation of a lignin model for improved delignification procedures, J. Mol. Catal. B: Enzymatic 26 (2003) 105–10;

27) Bast A., Haenen G.R., Doelman C.J., Oxidants and antioxidants: state of the art, Am. J. Med. 91 (1991) 2–13;

28) Bauer C.G., Kuehn A., Gajovic N., Skorobogatko O., Holt P.J., Bruce N.C., Makower A., Lowe C.R., Scheller F.W., New enzyme sensors for morphine and codeine based on morphine dehydrogenase and laccase, Fresenius J. Anal. Chem. 364 (1999) 179–183;

29) Bayrakçeken F., Aktas S., Toptan M., Unlugedik A., High resolution electronic absorption spectra of anisole and phenoxyl radical, Spectrochim. Acta 59 (2003) 135–138;

30) Beek T.A., Kuster B., Claassen F.W., Tienvieri T., Bertaud F., Lenon G., Fungal bio-treatment of sprucewood with Trametes versicolor for pitch control: Influence on extractive contents, pulping process parameters, paper quality and effluent toxicity, Biores.Technol. 98 (2007) 302–11;

31) Bento I., Martins L.O., Lopes G.G., Carrondo M.A., Lindley P.F., Dioxygen reduction by multi-copper oxidases; a structural perspective, Dalton. Trans. 21 (2005) 3507-3513;

32) Bent, I., Silva C.S., Chen Z., Martins L.O., Lindley P.F., Soares C.M., Mechanisms underlying dioxygen reduction in laccases. Structural and modelling studies focusing on proton transfer, BMC Struct. Biol. 10 (2010) 28-32;

33) Bertrand G., Sur la laccase et sur le pouvoir oxydant de cette diastase, Reports of the Paris Academy of Sciences (Paris) 120 (1895) 266–269;

34) Bernardi A.P.M., Lopez-Alarcon C., Aspee A., Rech S., Von Poser G.L., Bride R., Lissp E. Antioxidant activity of flavonoids isolated from Hypericum ternum, J. Chilean Chem. Soc., 52 (2007) 1326-1329;

35) Binz T., Canevascini G., Differential production of laccases in Dutch elm disease pathogens Ophiostoma ulmi and O. novo-ulmi, Mycol. Res. 100 (1996) 1060–1064;

36) Bloom M., Van Zyl W.H., Joubert E., Botha A., De Villiers D., Patent number WO2006013530 (2006);

37) Boland G.J., Hall R., Index of plant hosts of Sclerotinia sclerotiorum, Canad. J. Plant Pathol. 16 (1994) 93–108;

38) Bolton D.M., Thomma B.P.H.J., Nelson B.D., Sclerotinia sclerotiorum (Lib.) de Bary: biology and molecular traits of a cosmopolitan pathogen, Molec. Plant Pathol. 7 (2006) 1–16;

39) Bourbonnais R., Paice M.G., Reid I.D., Lanthier P., Yaguchi M., Lignin oxidation by laccase isozymes from Trametes versicolor and role of the mediator 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) in kraft lignin depolymerization, App. Envir. Microbiol. 61 (1995) 1876–1880;

40) Bourbonnais R., Paice M.G., Demethylation and delignification of kraft pulp by Trametes versicolor laccase in the presence of 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) acid, Appl. Microbiol. Biotechnol. 36 (2004) 823-827;

41) Brand-Williams W., Cuvelier M.E., Berset C., Use of a free radical method to evaluate antioxidant activity, Lebensmittel-Wissenschaft Technol., 28 (1995) 25-30;

42) Briciu R.D., Kot-Wasik A., Namiesnik J., Sarbu C., The lipophilicity indices of flavonoids estimated by reversed-phase liquid chromatography using different computation methods, J. Sep. Sci. 32(2009) 2066–2074;

43) Briciu R.D., Sarbu C., Lipophilicity of flavonoids estimated by reversed-phase high performance thin-layer chromatography: chemically bonded plates vs. impregnated plates with oils, animal, and human fats, Separ. Sci. Technol. 45 (2010) 1275–1285;

44) Brijwani K., Rigdon A., Vadlani P.V., Fungal laccases: production, function, and applications in food processing, Enzyme Res. (2010), ID 149748, 10 pages;

45) Brouwers G.-J., de Vrind J.P., Corstiens P.L., Cornelis P., Baysse C., de Vrind-de Jong E.W., CumA, a gene encoding a multicopper oxidase, is involved in Mn²⁺ oxidation in Pseudomonas putida GB-1, Appl. Environ. Microbiol. 65 (1999) 1762–1768;

46) Buijs W., Comba P., Corneli D., Pritzkow H., Structural and mechanistic studies of the copper(II)-assisted ortho-hydroxylation of benzoates by trimethylamine N-oxide, J. Organomet. Chem. 641 (2002) 71-80;

47) Bukh C., Lund M., Bjerrum M.J., Kinetic studies on the reaction between Trametes villosa laccase and dioxygen, J. Inorg. Biochem., 100 (2006) 1547–1557;

48) Bulter T., Alcalde M., Sieber V., Meinhold P., Schlachtbauer C., Arnold F.H., Functional expression of a fungal laccase in Saccharomyces cerevisiae by directed evolution, Appl. Environ. Microbiol. 69 (2003) 987–995;

49) Burda S., Oleszek W., Antioxidant and antiradical activities of flavonoids, J. Agric. Food Chem. 49 (2001) 2774–2779.

50) Burdock G.A., Review of the biological properties and toxicity of propolis, Food Chem. Toxicol., 36 (1998) 341–363;

51) Buswell J.A., Cai Y., Chang S., Effect of nutrient nitrogen and manganese on laccase production by L. edodes, FEMS Microbiol. Lett. 128 (1995) 81-88;

52) Calcaterra A., Galli C., Gentili P., Phenolic compounds as likely natural mediators of laccase: A mechanistic assessment, J. Mol. Catal. B: Enzym. 51 (2008) 118–120;

53) Calle C., Schweiger A., Mitrikas G., Continuous-wave and pulse EPR study of the copper(II) complex of N-confused tetraphenylporphyrin: direct observation of a sigma metal-carbon bond, Inorg. Chem. 46 (2007) 1847-55;

54) Canada A.T., Giannella E., Nguyen T.D., Mason R.P., The production of reactive oxygen species by dietary flavonols, Free Radic. Biol. Med. 9 (1990) 441–449;

55) Cao G., Prior R.L., Anthocyanins are detected in human plasma after oral administration of an elderberry extract, Clin. Chem. 45 (1999) 574-576;

56) Cao G., Sofic E., Prior R.L., Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships, Free Radic. Biol. Med. 22 (1997) 749–760;

57) Cessna S.G., Sears V.E., Dickman M.B., Low P.S., Oxalic acid, a pathogenicity factor for Sclerotinia sclerotiorum, suppresses the oxidative burst of the host plant, The Plant Cell 2 (2000) 2191–2199;

58) Chakroun H., Mechichi T., Jesus Martinez M., Dhouib A., Sayadi S., Purification and characterization of a novel laccase from the ascomycete Trichoderma atroviride: Application on bioremediation of phenolic compounds, Process Biochem. 45 (2010) 507–513;

59) Chan T., Galati G., O'Brien P.J., Oxygen activation during peroxidase catalysed metabolism of flavones or flavanones, Chem. Biol. Interact. 122 (1999) 15–25;

60) Chen C.C., Hwang J.K., Yang J.M., (PS)2-v2: template-based protein structure prediction server, Bioinformatics 10 (2009) 366-379;

61) Chen Z., Durão P., Silva C.S., Pereira M.M., Todorovic S., Hildebrandt P., Bento I., Lindley P. F., Martins L.O., The role of Glu498 in the dioxygen reactivity of CotA-laccase from Bacillus subtilis, Dalton. Trans. 39 (2010) 2875-2882;

62) Chernykh A., Myasoedova N., Kolomytseva M., Ferraroni M., Briganti F., Scozzafava A., Golovleva L., Laccase isoforms with unusual properties from the basidiomycete Steccherinum ochraceum strain 1833, J. Appl. Microbiol. 105 (2008) 2065–2075;

63) Christenson A., Dimcheva N., Ferapontova E.E., Gorton L., Ruzgas T., Stoica L., Shleev S., Yaropolov A.I., Haltrich D., Thorneley R.N.F., Austf S.D., Direct Electron Transfer Between Ligninolytic Redox Enzymes and Electrodes, Electroanal. 16 (2004) 13-14;

64) Clark P.A., Solomon E.I., Magnetic circular dichroism spectroscopic definition of the intermediate produced in the reduction of dioxygen to water by native laccase, J. Am. Chem. Soc. 114 (1992) 1108–1110;

65) Clark K., Penner-Hahn J.E., Whittaker M.M., Whittaker J.W., Oxidation-state assignments for galactose oxidase complexes from x-ray absorption spectroscopy. Evidence for copper(II) in the active enzyme, J. Am. Chem. Soc. 112 (1990) 6433-6434;

66) Claus H., Laccases: structure, reactions, distribution, Micron 35 (2004) 93–96;

67) Colao M.C., Garzillo A.M., Buonocore V., Schiesser A., Ruzzi M., Primary structure and transcription analysis of a laccase encoding gene from the basidiomycete Trametes trogii, Appl. Microbiol. Biotechnol. 63 (2003) 153-158;

68) Coll P.M., Fernandez-Abalos J.M., Villanueva J.R., Santamarıa R., Perez P., Purification and characterization of a phenoloxidase (laccase) from the lignin-degrading Basidiomycete PM1 (CECT 2971), Appl. Environ. Microbiol. 59 (1993) 2607–2613;

69) Comba P., Knoppe S., Martin B., Rajaraman G., Rolli C., Shapiro B., Stork T., The copper(II)-mediated aromatic ortho-hydroxylation: A hybrid DFT and ab initio exploration, Chem. Eur. J. 14 (2008) 344-357;

70) Conrad L.S., Sponholz W.R., Berker O., Treatment of cork with a phenol oxidizing enzyme, patent number US6152966 (2000);

71) Cooper C.E., Silaghi-Dumitrescu R., Rukengwa M., Alayash A.I., Buehler P.W., Peroxidase activity of hemoglobin towards ascorbate and urate: a synergistic protective strategy against toxicity of Hemoglobin-Based Oxygen Carriers (HBOC), Biochim. Biophys. Acta 1784 (2008) 1415-1420;

72) Corpet F., Multiple sequence alignment with hierarchical clustering, Nucl. Acids Res. 16 (1988) 10881-10890;

73) Couto S.R., Toca-Herrera J.L., Laccase production at reactor scale by filamentous fungi, Biotechnol. Adv. 25 (2007) 558–569;

74) Couto S.R., Herrera J.L.T., Industrial and biotechnological applications of laccases: A review, Biotechnol. Adv. 24 (2006) 500–513;

75) Crestini C., Perazzini R., Saladino R., Oxidative functionalisation of lignin by layer-by-layer immobilised laccases and laccase microcapsules, Appl. Catal. A: General 372 (2010) 115–123;

76) Crowe J.D., Olsson S., Induction of laccase activity in Rhizoctonia solani by antagonistic Pseudomonas fluorescens strains and a range of chemical treatments, Appl. Envir. Microbiol. 67 (2001) 2088–2094;

77) De Souza C.G.M., Peralta R.M., Purification and characterization of the main laccase produced by the white-rot fungus Pleurotus pulmonarius on wheat bran solid state medium, J. Basic. Microbiol. 43 (2003) 278–286;

78) Dean J.F.D., LaFayette P.R., Rugh C., Tristram A.H., Hoopes J.T., Eriksson K.-E.L., Merkle S.A., Laccases associated with lignifying vascular tissues. In: Lewis N.G., Sarkanen S. (Eds.), Lignin and Lignan Biosynthesis, ACS Symposium Series 697, American Chemical Society, Washington, DC, (1998) p. 96;

79) Decker A., Solomon E.I., Dioxygen activation by copper, heme and non-heme iron enzymes: comparison of electronic structures and reactivities, Curr. Opin. Chem. Biol. 9 (2005) 152-163;

80) Ducros V., Brzozowski A.M., Wilson K.S., Brown. S.H., Ostergaard P., Schneider P., Yaver D.S., Pedersen A.H., Davies G.J., Crystal structure of the type-2 Cu depleted laccase from Coprinus cinereus at 2.2 A resolution, Nat. Struct. Biol. 5 (1998) 310-316;

81) Dueñas M., González-Manzano S., González-Paramás A., Santos-Buelga C., Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin, J. Pharm. Biomed. Anal. 51 (2001) 443–449;

82) Dunne J., Caron A., Menu P., Alayash A.I., Buehler P.W., Wilson M.T., Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivo, Biochem. J. 399 (2006) 513-24;

83) Dunne J., Svistunenko D.A., Alayash A.I., Wilson M.T., Cooper C.E., Reactions of cross-linked methaemoglobins with hydrogen peroxide, Adv. Exp. Med. Biol. 471 (1999) 9-15;

84) Durao P., Chen Z., Fernandes A.T., Hildebrandt P., Murgida D.H., Todorovic S., Pereira M.M., Melo E.P., Martins L.O., Copper incorporation into recombinant CotA laccase from Bacillus subtilis: characterization of fully copper loaded enzymes, J. Biol. Inorg. Chem. 13 (2008) 183–193;

85) Durman S.B., Menendez A.B., Godeas A.M., Variation in oxalic acid production and mycelial compatibility within field populations of Sclerotinia sclerotiorum, Soil Biol. Biochem. 37 (2005) 2180–2184;

86) Edens W.A., Goins T.Q., Dooley D., Henson J.M., Purification and characterization of a secreted laccase of Gaeumannomyces graminis var. tritici., Appl. Environ. Microbiol. 65 (1999) 3071-3074;

87) Edens W.A., Goins T.Q., Dooley D., Henson J.M., Purification and characterization of a secreted laccase of Gaeumannomyces graminis var. tritici, Appl. Environ. Microbiol. 65 (1999) 3071–3074;

88) Eggert C., Temp U., Eriksson K.E., The ligninolytic system of the white rot fungus Pycnoporus cinnabarinus: purification and characterization of the laccase, Appl. Envir. Microbiol. 62 (1996) 1151–1158;

89) Ehlinger N., Scheidt W.R., Structure and apparent reactivity of the pi-cation radical derivatives of zinc and copper 5,10,15,20-tetra(2,6-dichlorophenyl)porphyrinate, Inorg. Chem. 38 (1999) 1316-1321;

90) Eisenman C.H., Mues M., Weber S.E., Frases S., Chaskes S., Gerfen G., Casadevall A., Cryptococcus neoformans laccase catalyses melanin synthesis from both d- and l-DOPA, Microbiology 153 (2007) 3954–3962;

91) Elisashvili V., Kachlishvili E., Physiological regulation of laccase and manganese peroxidase production by white-rot Basidiomycetes, J. Biotechnol.144 (2009) 37–42;

92) Enguita F.J., Marc D.¸ Martins L.O., Grenha R., Henriques A.O., Lindley P.F., Carrondo M.A., Substrate and dioxygen binding to the endospore Coat laccase from Bacillus subtilis, J. Biol. Chem. 279 (2004) 23472–23476;

93) Enguita F.J., Martins L.O., Henriques A.O., Carrondo M.A., Crystal structure of a bacterial endospore coat component, J. Biol. Chem. 278 (2003) 19416–19425

94) Erental A., Dickman M.B., Yarden O., Sclerotial development in Sclerotinia sclerotiorum: awakening molecular analysis of a ‘‘dormant’’ structure, Fungal Biol. Rev. 22 (2008) 6–16;

95) Espin J.C., Soler-Rivas C., Wichers H.J., Characterization of the total free radical scavenger capacity of vegetable oils and oil fractions using 2,2-diphenyl-1-picrylhydrazyl radical, J. Agric. Food Chem. 48 (2000) 648-656;

96) Espin J.C., Soler-Rivas C., Wichers H.J., Characterization of the total free radical scavenger capacity of vegetables oils and oil fractions using 2,2diphenyl-1-picrylhydrazyl radical, J. Agric. Food Chem. 48 (2000) 648-656;

97) Fackler K., Kuncinger T., Ters T., Srebotnik E., Laccase-catalyzed functionalization with 4-hydroxy-3-methoxybenzylurea significantly improves internal bond of particle boards, Holzforschung 62 (2008) 223-229;

98) Fakoussa R.M., Frost P.J., In vivo-decolorization of coalderived humic acids by laccase-excreting fungus Trametes versicolor, Appl. Microbiol. Biotechnol. 52 (1999) 60–65;

99) Faraco V., Ercole C., Festa G., Giardina P., Piscitelli A., Sannia G., Heterologous expression of heterodimeric laccase from Pleurotus ostreatus in Kluyveromyces lactis, Appl. Microbiol. Biotechnol. 77 (2008) 1329–1335;

100) Fernandez-Larrea J., Stahl U., Isolation and characterization of a laccase gene from Podospora anserina, Mol. Gen. Genet. 252 (1996) 539–551;

101) Ferrali M., Signorini C., Caciotti B., Sugherini L., Ciccoli L., Giachetti D., Comporti M., Protection against oxidative damage of erythrocyte membranes by the flavonoid quercetin and its relation to iron chelating activity, FEBS Lett. 416 (1997) 123–129;

102) Ferraroni M., Myasoedova N.M., Schmatchenko V., Leontievsky A.A., Golovleva L.A., Scozzafava A., Briganti F., Crystal structure of a blue laccase from Lentinus tigrinus: evidences for intermediates in the molecular oxygen reductive splitting by multicopper oxidases, BMC Struct. Biol. 7 (2007) 60;

103) Fogliano V., Monti S.M., Musella T., Randazzo G., Ritieni A., Formation of coloured Maillard reaction products in a gluten-glucose model system, Food Chem. 66 (1999) 293-299;

104) Forootanfar H., Faramarzi M.A., Shahverdi A.R., Yazdia M.T., Purification and biochemical characterization of extracellular laccase from the ascomycete Paraconiothyrium variabile, Bioresour. Technol. 102 (2011) 1808-1814;

105) Fowler Z.L., Baron C.M., Panepinto J.C., Koffas M.A.G., Melanization of flavonoids by fungal and bacterial laccases, Yeast 28 (2011) 181-188;

106) Frei B., Higdon J.V., Antioxidant activity of tea polyphenols in vivo: evidence from animal studies, J. Nutr. 133 (2003) 3275-3284;

107) Freire R.S., Duran N., Wang J., Kubota L.T., Laccase-based screen printed electrode for amperometric detection of phenolic compounds, Anal. Lett. 35 (2002) 29-38;

108) Froehner S.C., Eriksson K.-E., Purification and properties of Neurospora crassa laccase, J. Bacteriol. 120 (1974) 458–465;

109) Fukumoto L.R., Mazza G., Assessing antioxidant and prooxidant activities of phenolic compounds, J. Agric. Food Chem. 48 (2000) 3597-3604;

110) Galati G., Chan T., Wu B., O'Brien P.J., Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids, Chem. Res. Toxicol. 12 (1999) 521–525;

111) Galati G., Moridani M.Y., Chan T.S., O’Brien P.J., Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation, Free Radic. Biol. Med. 30 (2001) 370–382;

112) Galati G., Sabzevari O., Wilson J.X., O'Brien P.J., Prooxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics, Toxicology 177 (2002) 91–104;

113) Galati G., Teng S., Moridani M.Y., Chan T.S., O’Brien P.J., Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics, Drug Metab. Drug Interact. 17 (2000) 311–349;

114) Galhaup C., Goller S., Peterbauer C.K., Strauss J., Haltrich D., Characterization of the major laccase isoenzyme from Trametes pubescens and regulation of its synthesis by metal ions, Microbiology 148 (2002) 2159–2169;

115) Galhaup C., Haltrich D., Enhanced formation of laccase activity by the white-rot fungus Trametes pubescens in the presence of copper, Appl. Microbiol. Biotechnol. 56 (2001) 225-232;

116) Gallaway J., Wheeldon I., Rincon R., Atanassov P., Banta S., Barton S. C., Oxygen-reducing enzyme cathodes produced from SLAC, a small laccase from Streptomyces coelicolor, Biosens. Bioel. 23 (2008) 1229-1235;

117) Gamache P.H., Acworth I.N., Analysis of phytoestrogens and polyphenols in plasma, tissue, and urine using HPLC with coulometric array detection, Exp. Biol. Med. 217 (1998) 274-280;

118) Garavaglia S., Cambria M.T., Miglio M., Ragusa S., Iacobazzi V., Palmieri F., D’Ambrosio C., Scaloni A., Rizzi M., The structure of Rigidoporus lignosus laccase containing a full complement of copper ions, reveals an asymmetrical arrangement for the T3 copper pair, J. Mol. Biol. 342 (2004) 1519–1531;

119) Gayazov R., Rodakiewicz-Nowak J., Semi-continuous production of laccase by P. radiata in different culture media, Folia Microbiol. 41 (1996) 480-484;

120) Germann U., Muller G., Hunziker P., Lerch K., Characterization of two allelic forms of Neurospora crassa laccase. Amino- and carboxyl-terminal processing of a precursor, J. Biol. Chem. 263 (1988) 885–896;

121) Ghindilis A.L., Gavrilova V.P., Yaropolov A. I., Laccase-based biosensor for determination of polyphenols: determination of catechols in tea, Biosens. Bioelectron.7 (1992) 127-131;

122) Giardina P., Autore F., Faraco V., Festa G., Palmieri G., Piscitelli A., Sannia G., Structural characterization of heterodimeric laccases from Pleurotus ostreatus, Appl. Microbiol. Biotechnol. 75 (2007) 1293–1300;

123) Giardina P., Faraco V., Pezzella C., Piscitelli A., Vanhulle S., Sannia G., Laccases: a never-ending story, Cell. Mol. Life Sci. 67 (2010) 369–385;

124) Givaudan A., Effosse A., Faure D., Potier P., Bouillant M.L., Bally R., Polyphenol oxidase in Azospirillum lipoferum isolated from rice rhizosphere: evidence for a laccase in non-motile strains of Azospirillum lipoferum, FEMS Microbiol. Lett. 108 (1993) 205–210;

125) Gnanamani A., Jayaprakashvel M., Arulmani M., Sadulla S., Effect of inducers and culturing processes on laccase synthesis in Phanerochaete chrysosporium NCIM 1197 and the constitutive expression of laccase isozymes, Enzyme Microbiol. Technol. 38 (2006) 1017–1021;

126) Goldman R., Claycamp R., Sweetland G.H., Sedlov M.A., Tyurin A.V., Kisin E.R., Tyurina Y.Y., Ritov V.B., Wenger S.L., Grant S.G., Kagan V.E., Myeloperoxidase-catalyzed redox-cycling of phenol promotes lipid peroxidation and thiol oxidation in HL-60 cells, Free Radic. Biol. Med. 27 (1999) 1050–1063;

127) Golz-Berner K., Walzel B., Zastrow L., Doucet O., Cosmetic and dermatological preparation containing copperbinding proteins for skin lightening, Patent number WO2004017931 (2004);

128) Gomes S.A., Nogueira J.M.F., Rebelo M.J.F., An amperometric biosensor for polyphenolic compounds in red wine, Biosens. Bioel. 20 (2004) 1211-1216;

129) González-Forero D., Alvarez F.J., Differential postnatal maturation of GABAA, glycine receptor, and mixed synaptic currents in renshaw cells and ventral spinal interneurons, J. Neuroscience 25 (2005) 2010-2023;

130) Gorbacheva M., Morozova O., Shumakovich G., Streltsov A., Shleev S., Yaropolov A., Enzymatic oxidation of manganese ions catalysed by laccase, Bioorg. Chem. 37 (2009) 1–5;

131) Gray H.B., Malmstrom B.G., Williams R.J., Copper coordination in blue proteins, J Biol. Inorg. Chem. 5 (2000) 551–559;

132) Groves J.T., High-valent iron in chemical and biological oxidations, J. Inorg. Biochem. 100 (2006) 434-47;

133) Guzy C.M., Raynor J.B., Stodulski L.P., Symons M.C., Electron spin resonance spectra of chromium, iron, nickel, copper and metal-free phthalocyanine reduced by sodium in tetrahydrofuran and in hexamethylphosphoramide, J. Chem. Soc. (1969) 997-1001;

134) Haibo Z., Yinglong Z., Feng H., Peiji G., Jiachuan C., Purification and characterization of a thermostable laccase with unique oxidative characteristics from Trametes hirsuta, Biotechnol. Lett. 31 (2009) 837–843;

135) Hakulinen N., Kruus K., Koivula A., Rouvinen J., A crystallographic and spectroscopic study on the eﬀect of X-ray radiation on the crystal structure of Melanocarpus albomyces laccase, Biochem. Biophys. Res. Comm. 350 (2006) 929–934;

136) Hakulinen N., Andberg M., Kallio J., Koivula A., Kruus K., Rouvinen J., A near atomic resolution structure of a Melanocarpus albomyces laccase, J. Struct. Biol. 162 (2008) 29–39;

137) Halliwell B., Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?, Arch. Biochem. Biophys. 476 (2008) 107–112;

138) Hamilton G.A., Adolf P.K., De Jersey J., DuBois G.C., Dyrkacz G.R., Libby R.D., Trivalent copper, superoxide, and galactose oxidase, J. Am. Chem. Soc. 100 (1978) 1899-1912;

139) Han S.K., Park H.K., A study on the preservation of meat products by natural propolis: effect of EEP on protein change of meat products, K. J. A. Science, 37 (1995) 551–557;

140) Hanasaki Y., Ogawa S., Fukui S., The correlation between active oxygens scavenging and antioxidative effects of flavonoids, Free Radic. Biol. Med. 16 (1994) 845–850;

141) Hao J., Song F., Huang F., Yang C., Zhang Z., Zheng Y., Tian, X., Production of laccase by a newly isolated deuteromycete fungus Pestalotiopsis sp. and its decolorization of azo dye, J. Ind. Microbiol. Biotechnol. 34 (2007) 233–240;

142) Hassett R.F., Yuan D.S., Kosman D.J., Spectral and kinetic properties of the Fet3 protein from Saccharomyces cerevisiae, a multicopper ferroxidase enzyme, J. Biol. Chem. 273 (1998) 23274–23282;

143) Hattori M., Tsuchihara K., Noda H., Konishi H., Tamura Y., Shinoda T., Nakamura M., Hasegawa T., Molecular characterization and expression of laccase genes in the salivary glands of the green rice leafhopper, Nephotettix cincticeps (Hemiptera: Cicadellidae), Insect. Biochem. Mol. Biol. 40 (2010) 331-338;

144) Hattori M., Konishi H., Tamura Y., Konno K., Sogawa K., Laccase-type phenoloxidase in salivary glands and watery saliva of the green rice leafhopper, Nephotettix cincticeps, J. Insect Physiol. 51 (2002)1359–1365;

145) Heim K.E., Tagliaferro A.R., Bobilya D.J., Flavonoid antioxidants: chemistry, metabolism and structure–activity relationships, J. Nutr. Biochem. 13 (2002) 572–584;

146) Heinzkill M., Bech L., Halkier T., Schneider P., Anke T., Characterization of laccase and peroxidase from wood-rotting fungi, Appl. Envir. Microbiol. 64 (1998) 1601-1606;

147) Hess A.V.I., Digitally enhanced thin-layer chromatography: an inexpensive, new technique for qualitative and quantitative analysis, J. Chem. Ed. 84 (2007) 842-847;

148) Hilden K., Hakaa T.K., Lundell T., Thermotolerant and thermostable laccases, Biotechnol. Lett. 31 (2009) 1117–1128;

149) Hirose J., Nasu M., Yokoi H., Reaction of substituted phenols with thermostable laccase bound to Bacillus subtilis spores, Biotechnol. Lett. 25 (2003) 1609-1612;

150) Hkulinen N., Kiiskinen L.L., Kruus K., Saloheimo M., Paananen A., Koivula A., Rouvinen J., Crystal structure of a laccase from Melanocarpus albomyces with an intact trinuclear copper site, Nat. Struct. Biol. 9 (2002) 601-605;

151) Hodnick W.F., Duval D.L., Pardini R.S., Inhibition of mitochondiral respiration and cyanide-stimulated generation of reactive oxygen species by selected flavonoids, Biochem. Pharmacol. 47 (1994) 573–580;

152) Hölker U., Dohse J., Höfer M., Extracellular laccases in ascomycetes Trichoderma atroviride and Trichoderma harzianum, Folia Microbiol. 47 (2002) 423-427;

153) Hollman P.C., van Trijp J.M., Buysman M.N., van der Gaag M.S., Mengelers M.J., de Vries J.H., Katan M.B., Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man, FEBS Lett. 418 (1997) 152–156;

154) Huang H., Zoppellaro G., Sakurai T., A novel mixed valence form of Rhus vernicifera laccase and its reaction with dioxygen to give a peroxide intermediate, J. Biol. Chem. 274 (1999) 32718–32724;

155) Huang D., Ou B., Prior R.L., The chemistry behind antioxidant capacity assays, J. Agr. Food Chem. 53 (2005) 1841-1856;

156) Huang W.T., Tai R., Hseu R.S., Huang C.T., Overexpression and characterization of a thermostable, pH-stable and organic solvent-tolerant Ganoderma fornicatum laccase in Pichia pastoris, Process Biochem. 46 (2011) 1469–1474;

157) Huttermann A., Mai C., Kharazipour A., Modification of lignin for the production of new compounded materials, Appl. Microbiol. Biotechnol. 55 (2001) 387–394;

158) Hyperchem(TM) Molecular Modelling System, Release 5.01 for Windows, Hypercube, Inc. (1998);

159) Inamo M., Kumagai H., Harada U., Itoh S., Iwatsuki S., Ishihara K., Takagi H.D., Electron transfer reactions between copper(II) porphyrin complexes and various oxidizing reagents in acetonitrile, Dalton Trans. (2004) 1703-1707;

160) Ivona J., Mirza B., Ana M., Erim B., Kajo B., Marica M.S., Evaluation of antioxidative activity of Croatian propolis samples using DPPH? and ABTS²⁺ stable free radical assays, Molecules 12 (2007) 1006-1021;

161) Jasprica I., Bojic M., Mornar A., Besic E., Bucan K., Medic-Saric M., Evaluation of antioxidative activity of Croatian propolis samples using DPPH· and ABTS·²⁺ stable free radical assays, Molecules, 12 (2007) 1006-1021;

162) Jeon J.-R., Baldrian P., Murugesan K., Chang Y.-S., Laccase-catalysed oxidations of naturally occurring phenols: from in vivo biosynthetic pathways to green synthetic applications, Microb. Biotechnol. 5 (2011) 318-332;

163) Johansson M., Denekamp M., Asiegbu F.O., Production and isozyme pattern of extracellular laccase in the S and P intersterility groups of the root pathogen Heterobasidion annosum, Mycol. Res. 103 (1999) 365–371;

164) Jones D., Ultrastructure and composition of the cell walls of Sclerotinia sclerotiorum, Trans. Brit. Mycol. Soc. 54 (1970) 351–360;

165) Jørgensen L.V., Madsen H.L., Thomsen M.K., Dragsted L.O., Skibsted L.H., Regeneration of phenolic antioxidants from phenoxyl radicals: An ESR and electrochemical study of antioxidant hierarchy, Free Rad. Res. 30 (1999) 207-220;

166) Josephygg P.D., Elingg T., Mason R.P., The horseradish peroxidase-catalyzed oxidation of 3,5,3’,5’-tetramethylbenzidine, J. Biol. Chem. 257 (1982) 3669- 3675;

167) Jovanovic S.V., Steenken S., Hara Y., Simic M.G., Reduction potentials of flavonoid and model phenoxyl radicals. Which ring in flavonoids is responsible for antioxidant activity?, J. Chem. Soc. Perkin Trans. 2 (1996) 2497-2504;

168) Jung H., Xu F., Li K., Purification and characterization of laccase from wood-degrading fungus Trichophyton rubrum. LKY-7, Enzyme Microb. Technol. 30 (2002) 161-168;

169) Junghanns C., Pecyna M.J., Bohm D., Jehmlich N., Martin C., von Bergen M., Schauer F., Hofrichter M., Schlosser D., Biochemical and molecular genetic characterisation of a novel laccase produced by the aquatic ascomycete Phoma sp. UHH 5-1-03, Appl. Microbiol. Biotechnol. 84 (2009) 1095-105;

170) Justino G.C., Santos M.R., Canário S., Borges C., Florêncio M.H., Mira L., Plasma quercetin metabolites: structure−antioxidant activity relationships, Arch. Biochem. Biophys. 432 (2004) 109–121;

171) Kallio J.P., Gasparetti C., Andberg M., Boer H., Koivula A., Kruus K., Rouvinen J., Crystal structure of an ascomycete fungal laccase from Thielavia arenaria: Common structural features of asco-laccases, FEBS J. 278 (2011) 2283–2295.

172) Kamachi T., Kihara N., Shiota Y., Yoshizawa K., Computational exploration of the catalytic mechanism of dopamine beta-monooxygenase: modeling of its mononuclear copper active sites, Inorg. Chem. 44 (2005) 4226-4236;

173) Kaneko S., Cheng M., Murai H., Takenaka S., Murakami S., Aoki K., Purification and characterization of an extracellular laccase from Phlebia radiata strain BP-11-2 that decolorizes fungal melanin, Biosci. Biotechnol. Biochem. 73 (2009) 939–942;

174) Kartal M., Yıldız S., Kaya S., Kurucu S., Topçu G., Antimicrobial activity of propolis samples from two different regions of Anatolia, J. Ethnopharmacol. 86 (2003) 69-73;

175) Kataoka K., Sugiyama R., Hirota S., Inoue M., Urata K., Minagawa Y., Seo D., Sakurai T., Four-electron reduction of dioxygen by a multicopper oxidase, CueO, and roles of Asp112 and Glu506 located adjacent to the trinuclear copper center, J. Biol. Chem., 284 (2009) 14405–14413;

176) Katircioglu H., Mercan N., Antimicrobial activity and chemical compositions of Turkish propolis from different region, Afric. J. Biotechnol. 5 (2006) 1151-1153;

177) Kiiskinen L.-L., Saloheimo M., Molecular cloning and expression in Saccharomyces cerevisiae of a laccase gene from the ascomycete Melanocarpus albomyces, Appl. Environ. Microbiol. 70 (2004) 137–144;

178) Kim H., Chen C., Kabbage M., Dickman M.B., Identification and characterization of Sclerotinia sclerotiorum NADPH oxidases, Appl. Environ. Microbiol. 77 (2011) 7721-7729;

179) Kitajima N., Moro-oka Y., Copper-Dioxygen Complexes. Inorganic and Bioinorganic Perspectives, Chem. Rev. 94 (1994) 737-757.

180) Klinman J.P., Mechanisms whereby mononuclear copper proteins functionalize organic substrates, Chem. Rev. 96 (1996) 2541–2562;

181) Klonowska A., Gaudin C., Fournel A., Asso M., Le Petit J., Giorgi M., Characterization of a low redox potential laccase from the basidiomycete C30, Eur. J. Biochem. 269 (2002) 6119–6125;

182) Koren E., Kohen R., Ginsburg I., Polyphenols enhance total oxidant-scavenging capacities of human blood by binding to red blood cells, Exp. Biol. Med. (Maywood) 235 (2010) 689-699.

183) Kruus K., Kiiskinen L.-L., Saloheimo M., Hakulinen N., Rouvinen J., Paananen A., Linder M., Viikari L., Purification and characterisation of a novel laccase from the ascomycete Melanocarpus albomyces, Appl. Microbiol. Biotechnol., 59 (2002) 198-204;

184) Kumar S.V.S., Phale P.S., Durani S., Wangikar P.P., Combined sequence and structure analysis of the fungal laccase family, Biotechnol. Bioeng. 83 (2003) 386–394;

185) Kunamneni A., Camarero S., García-Burgos C., Plou F.J., Ballesteros A., Alcalde M., Engineering and Applications of fungal laccases for organic synthesis, Microb. Cell. Fact. 7 (2008a) 1-17;

186) Kunamneni A., Plou F.J., Ballesteros A., Alcalde M., Laccases and their applications: a Patent review, Recent. Pat. Biotechnol. 2 (2008b) 10-24;

187) Kyritsis P., Messerchmidt A., Huber R., Salmon G.A., Sykes A.G., Pulse-radiolysis studies on the oxidised form of the multicopper enzyme ascorbate oxidase: evidence for two intramolecular electron transfer steps, J. Chem. Soc. Dalton Trans. (1993) 731–735;

188) Lad L., Mewies M., Basran J., Scrutton N.S., Raven E.L., Role of histidine 42 in ascorbate peroxidase. Kinetic analysis of the H42A and H42E variants, Eur. J. Biochem. 269 (2002) 3182-3192;

189) Lam H.S., Proctor A., Howard L., Cho M.J., Rapid fruit extracts antioxidant capacity determination by fourier transform infrared spectroscopy, J. Food Science 70 (2005) 545-549;

190) Lang G., Cotteret J., Hair dye composition containing a laccase, (L'Oreal, Fr.). Int. Pat. Appl. Patent number WO9936036, (1999);

191) Larsson S., Cassland P., Jonsson L.J., Development of a Saccharomyces cerevisiae strain with enhanced resistance to phenolic fermentation inhibitors in lignocellulose hydrolysates by heterologous expression of laccase, Appl. Envir. Microbiol. 67 (2001) 1163–1170;

192) Leatham G.F., Stahmann M.A., Studies on the laccase of Lentinus edodes: specificity, localization and association with the development of fruiting bodies, J. Gen. Microbiol. 125 (1981) 147-157;

193) Lee S.K., George S.D., Antholine W.E., Hedman B., Hodgson K.O., Solomon E.I., Nature of the intermediate formed in the reduction of O2 to H2O at the trinuclear copper cluster active site in native laccase, J. Am. Chem. Soc. 124 (2002) 6180–6193;

194) Lee D.Y., Chang G.D., Electrolytic reduction: modification of proteins occurring in isoelectric focusing electrophoresis and in electrolytic reactions in the presence of high salts, Anal. Chem. 81 (2009) 3957–3964;

195) Lee E.R., Kang G.H., Cho S.G., Effect of flavonoids on human health: old subjects but new challenges, Recent Pat. Biotechnol. 1 (2007) 139-150;

196) Lee M.J., Wang Z.Y., Li H., Chen L., Sun Y., Gobbo S., Balentine D.A., Yang C.S., Analysis of plasma and urinary tea polyphenols in human subjects, Cancer Epidem. Biomar. Prev. 4 (1995) 393-399;

197) Lee-Hilz Y.Y., Boerboom A.M., Westphal A.H., Berkel W.J., Aarts J.M., Rietjens I.M., Pro-oxidant activity of flavonoids induces EpRE-mediated gene expression, Chem. Res. Toxicol. 19 (2006) 1499-1505;

198) Leontievsky A., Myasoedova N., Pozdnyakova N., Golovleva L., `Yellow' laccase of Panus tigrinus oxidizes non-phenolic substrates without electron-transfer mediators, FEBS Lett. 413 (2006) 446-448;

199) Leontievsky A.A., Myasoedova N.M., Baskunov B.P., Pozdnyakova N.N., Vares T., Kalkkinen N., Hatakka A.I., Golovleva L.A., Reactions of blue and yellow fungal laccases with lignin model compounds, Biochemistry (Mosc.) 64 (1999) 1150–1156;

200) Leontievsky A.A., Vares T., Lankinen P., Shergill J.K., Pozdnyakova N.M., Myasoedova, Kalkkinen N., Golovleva L.A., Cammack R., Thurston C.F., Hatakka A., Blue and yellow laccases of ligninolytic fungi, FEMS Microbiol. Lett. 156 (1997) 9–14.

201) Levasseur A., Saloheimo M., Navarro D., Andberg M., Pontarotti P., Kruus K., Record E., Exploring laccase-like multicopper oxidase genes from the ascomycete Trichoderma reesei: a functional, phylogenetic and evolutionary study, BMC Biochem. 11 (2010) 32;

202) Lindley P.F., Handbook of Metalloproteins, Marcel Dekker, Inc., New York, (2001) p. 763–811.

203) Liptak M.D., Fleischhacker A.S., Matthews R.G., Telser J., Brunold T.C., Spectroscopic and computational characterization of the base-off forms of cob(II)alamin, J. Phys. Chem. B 113 (2009) 5245-5254;

204) Liptak M.D., Brunold T.C., Spectroscopic and computational studies of Co1+cobalamin: spectral and electronic properties of the "superreduced" B12 cofactor, J. Am. Chem. Soc. 128 (2006) 9144-9156;

205) Lisov A.V., Zavarzina A.G., Zavarzin A.A., Leontievsky A.A., Laccases produced by lichens of the order Peltigerales, FEMS Microbiol. Lett. 275 (2007) 46–52;

206) Litthauer D., Jansen van Vuuren M., van Tonder A., Wolfaardt F.W., Purification and kinetics of a thermostable laccase from Pycnoporus sanguineus (SCC 108), Enzyme Microb. Technol. 40 (2007) 563–568;

207) Liu L., Tewari R.P., Williamson P.R., Laccase protects Cryptococcus neoformans from antifungal activity of alveolar macrophages, Infect. Immun. 67 (1996) 6034–6039;

208) Liu Y.T., Lu B.N., Xu L.N., Yin L.H., Wang X.N., Peng J.Y., Liu K.X., The antioxidant activity and hypolipidemic activity of the total flavonoids from the fruit of Rosa laevigata, Michx. Nat. Sci. 3 (2010) 175–783;

209) Lo S.C., Ho Y.S., Buswell J.A., Effect of phenolic monomers on the production of laccases by the edible mushroom Pleurotus sajor-caju, and partial characterization of a major laccase component, Mycologia 93 (2001) 413-421;

210) Lomascolo A., Record E, Herpoël-Gimbert I., Delattre M., Robert J.L., Georis J., Dauvrin T., Sigoillot J.C., Asther M., Overproduction of laccase by a monokaryotic strain of Pycnoporus cinnabarinus using ethanol as inducer, J. Appl. Microbiol. 94 (2003) 618–624;

211) Lotito S.B, Frei B., Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon?, Free Radic. Biol. Med. 41 (2006) 1727–1746;

212) Luna-Acosta A., Rosenfeld E., Amari M., Fruitier-Arnaudin I., Bustamante P., Thomas-Guyon H., First evidence of laccase activity in the Pacific oyster Crassostrea gigas, Fish Shellfish Immunol. 28 (2010) 719-726;

213) MacDonald-Wicks L.K., Wood L.G., Garg M.L., Methodology for the determination of biological antioxidant capacity in vitro: a review, J. Sci. Food Agr. 86 (2006) 2046-2056;

214) Maceiras R., Rodriguez C.S., Sanroman A., Influence of several activators on the extracellular laccase activity and in vivo decolourization of poly R-478 by semi-solid-state cultures of Trametes versicolor, Acta Biotechnol. 21 (2001) 255–264;

215) Machczynski M.C., Vijgenboom E., Samyn B., Canters G.W., Characterization of SLAC: A small laccase from Streptomyces coelicolor with unprecedented activity, Prot. Sci. 13 (2004) 2388–2397;

216) Machonkin T.E., Quintanar L., Palmer A.E., Hassett R., Severance S., Kosman D.J., Solomon E.I., Spectroscopy and reactivity of the type 1 copper site in Fet3p from Saccharomyces cerevisiae: Correlation of structure with reactivity in the multicopper oxidases, J. Am. Chem. Soc. 123 (2001) 5507–5517;

217) Mackiewicz A., Ratajczak W., Principal Component Analysis (PCA), Comp. Geosci., 19 (1993) 303-342;

218) Maeta K., Nomur W., Takashume Y., Izawa S., Inove Y., Green tea polyphenols fuction as prooxidants to active oxidative-stress-responsive transcription factors in yeasts, Appl. Environ. Microbiol. 73 (2007) 572–580;

219) Majeau J.A., Brar S.K., Tyagi R.D., Laccases for removal of recalcitrant and emerging pollutants, Biores. Technol. 101 (2010) 2331–2350;

220) Malkin R., Malmstrom B.G., Vanngard T., Spectroscopic differentiation of the electron-accepting sites in fungal laccase, Eur. J. Biochem. 10 (1969) 324–329;

221) Malmstrom B.G., Rack-induced bonding in blue-copper proteins, Eur. J. Biochem. 223 (1994) 711-718;

222) Manach C., Williamson G., Morand C., Scalbert A., Remesy C., Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies, Am. J. Clin. Nutr. 81 (2005) 230–242;

223) Mansur M., Suárez T., González A.E., Differential gene expression in the laccase gene family from basidiomycete I-62 (CECT 20197), App. Envir. Microbiol. 64 (1998) 771–774;

224) Manthey J.A., Fourier transform infrared spectroscopic analysis of the polymethoxylated flavone content of orange oil residues, J. Agr. Food Chem. 54 (2006) 3215-3218;

225) Mantovani T.R.D., Linde G.A., Colauto N.B., Effect of the addition of nitrogen sources to cassava fiber and carbon-to-nitrogen ratios on Agaricus brasiliensis growth, Canad. J. Microbiol. 53 (2007) 139-143;

226) Marcucci M.C., Propolis: chemical composition, biological properties and therapeutic activity, Apidology 26 (1995) 83-99;

227) Markham K.R., Mitchell K.A., Wilkins A.L., Daldy J.A., Lu Y., HPLC and GC-MS identification of the major organic constituents in New Zealand propolis, Phytochemistry 42 (1996) 205-211;

228) Martins L.O., Soares C.M., Pereira M.M., Teixeira M., Costa T., Jones G.H., Henriques A.O., Molecular and biochemical characterization of a highly stable bacterial laccase that occurs as a structural component of the Bacillus subtilis endospore coat, J. Biol. Chem. 277 (2002) 18849–18859;

229) Marukawa S., Funakawa S., Satomura Y., Role of sclerin on morphogenesis in Sclerotinia sclerotiorum de Bary (including S. libertiana Fuckel), Agr. Biol. Chem. 39 (1975) 645-650;

230) Matera I., Gullotto A., Tilli S., Ferraroni M., Scozzafava A., Briganti F., Crystal structure of the blue multicopper oxidase from the white-rot fungus Trametes trogii complexed with ptoluate, Inorgan. Chim. Acta 361 (2008) 4129–4137.

231) Mayera A.M., Staples R.C., Laccase: new functions for an old enzyme, Phytochemistry 60 (2002) 551–565;

232) Melníka M., Kabešová M., Cu(III) coordination compounds: classification and analysis of crystallographic and structural data, J. Coord. Chem. 50 (2000) 323- 328

233) Melo E.P., Fernandes A.T., Durao P., Martins L.O., Insight into stability of CotA laccase from the spore coat of Bacillus subtilis, Biochem. Soc. Trans. 35 (2007) 1579-82;

234) Mendonc R., Ferraz A., Kordsachia O., Koch G., Cellular UV microspectrophotometric investigations on pine wood (Pinus taeda and Pinus elliottii) delignification during biopulping with Ceriporiopsis subvermispora (Pilat) Gilbn. & Ryv. and alkaline sulfite/anthraquinone treatment, Wood Sci. Technol. 38 (2004) 567–75;

235) Menga F., Zuoa G., Haob X., Wangb G., Xiaob H., Zhangb J., Xua G., Antifungal activity of the benzo[c]phenanthridine alkaloids from Chelidonium majus Linn against resistant clinical yeast isolates, J. Ethnopharmacol. 125 (2009) 494–496;

236) Messerschmidt A., Multi-copper Oxidases, World Scientific, Singapore (1997);

237) Mimmi M.C., Gullotti M., Santagostini L., Battaini G., Monzani E., Pagliarin R., Zoppellaro G., Casella L., Models for biological trinuclear copper clusters. Characterization and enantioselective catalytic oxidation of catechols by the copper(II) complexes of a chiral ligand derived from (S)-(−)-1,1′-binaphthyl-2,2′-diamine, Dalton Trans. (2004) 2192-2201;

238) Min K.L., Kim Y.H., Kim Y.W., Jung H.S., Hah Y.C., Characterization of a novel laccase produced by the wood-rotting fungus Phellinus ribis, Arch. Biochem. Biophys. 392 (2001) 279–286;

239) Min K., Kim Y.H., Kim Y.W., Jung H.S., Hah Y.C., Characterization of a novel laccase produced by the wood-rotting fungus Phellinus ribis, Arch. Biochem. Biophys., 392 (2001) 279-286;

240) Minussi R.C., Pastore G.M., Duran N., Laccase induction in fungi and laccase/N-OH mediator systems applied in paper mill effluent, Bioresour. Technol. 98 (2007) 158–164;

241) Mirica L.M., Ottenwaelder X., Stack T.D., Structure and spectroscopy of copper-dioxygen complexes, Chem. Rev. 104 (2004) 1013-1045;

242) Miyataka H., Nishiki M., Matsumoto H., Fujimoto T., Matsuka M., Satoh T., Evaluation of Brazilian and Chinese propolis by enzymatic and physicochemical methods, Biol. Pharm. Bulletin, 20 (1997) 496–501;

243) Mizuno M., Food packaging materials containing propolis as a preservative, Japanese Patent No. JP Ol 243 974 [89 243 974] (1989);

244) Mladěnka P., Zatloukalová L., Filipský T., Hrdina R., Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity, Free Radic. Biol. Med. 15 (2010) 963–75.

245) Morozova O.V., Shumakovich G.P., Gorbacheva M.A., Shleev S.V., Yaropolov A.I., "Blue" laccases, Biochemistry (Mosc.) 72 (2007) 1136–1150;

246) Morozova O.V., Shumakovich G.P., Shleev S.V., Yaropolov Y.I., Laccase-mediator systems and their applications: A review, App. Biochem. Microb. 43 (2007) 523-535;

247) Moţ A.C., Damian G., Sarbu C., Silaghi-Dumitrescu R., Redox reactivity in propolis: direct detection of free radicals in basic medium and interaction with hemoglobin, Redox Rep. 14 (2009) 267-274;

248) Moţ A.C., Soponar F., Sârbu C., Multivariate analysis of reflectance spectra from propolis: geographical variation in Romanian samples, Talanta 81 (2010a) 1010-1015;

249) Moţ A.C., Kis Z., Svistunenko D.A, Damian G., Silaghi-Dumitrescu R., Makarov S.V., 'Super-reduced' iron under physiologically-relevant conditions, Dalton Trans. 39 (2010b) 1464-1466;

250) Moţ A.C., Silaghi-Dumitrescu R., Sarbu C., Rapid and effective evaluation of the antioxidant capacity of propolis extracts using DPPH bleaching kinetic profiles, FT-IR and UV–vis spectroscopic data, J. Food Comp. Anal. 24 (2011) 516–522;

251) Moţ A.C., Pârvu M., Damian G., Irimie F.D., Darula Z., Medzihradszky K.F., Brem B., Silaghi-Dumitrescu R., A “yellow” laccase with “blue” spectroscopic features, from Sclerotinia sclerotiorum, Process Biochem.47 (2012) 968–975;

252) Mougin C., Boyer F.D., Caminade E., Rama R., Cleavage of the diketonitrile derivative of the herbicide isoxaflutole by extracellular fungal oxidases, J. Agr. Food Chem. 48 (2000) 4529–4534;

253) Murugesan K., Chang Y.Y., Kim Y.M., Jeon J.R., Kim E.J., Chang Y.S., Enhanced transformation of triclosan by laccase in the presence of redox mediators, Water Res. 44 (2010) 298-308;

254) Nakagawa H.K., Hasumi J.T., Nagai K., Wachi M., Generation of hydroxide peroxide primarily contributes to the induction of Fe(II)-dependent apoptosis in Jurkat cells by (−)-epigallocatechin-3-gallate, Carcinogenesis 25 (2004) 1567–1574;

255) Nakamura K., Go N., Function and molecular evolution of multicopper blue proteins, Cell. Mol. Life Sci. 62 (2005) 2050–2066;

256) Neifar M., Jaouani A., Ellouze-Ghorbel R., Ellouze-Chaabouni S., Purification, characterization and decolourization ability of Fomes fomentarius laccase produced in solid medium, J. Mol. Cat. B: Enz. 64 (2010) 68–74;

257) Ness A.R., Powles J.W., Fruit and vegetables and cardiovascular disease: a review, Int. J. Epidemiol. 26 (1997) 1–13;

258) Ng T.B., Wang H.X, A homodimeric laccase with unique characteristics from the yellow mushroom Cantharellus cibarius, Biochem. Biophys. Res. Commun. 313 (2004) 37–41;

259) Niebisch C.H., Malinowski A.K., Schadeck R., Mitchell D.A., Kava-Cordeiro V., Paba J., Decolorization and biodegradation of reactive blue 220 textile dye by Lentinus crinitus extracellular extract, J. Hazard. Mater. 180 (2010) 316–322;

260) Nijveldt R.J., van Nood E., van Hoorn D.E.C., Boelens P.G., van Norren K., van Leeuwen P.A.M., Flavonoids: a review of probable mechanisms of action and potential applications, Am. J. Clin. Nutr. 74 (2001) 418–425;

261) Nun N.B., Lev A.T., Harel E., Mayer A.M., Repression of laccase formation in Botrytis cinerea and its possible relation to phytopathogenicity, Phytochemistry 27 (1988) 2505-2509;

262) Ohshima H., Yoshie Y., Auriol S., Gilibert I., Antioxidant and pro-oxidant actions of flavonoids: effects on DNA damage induced by nitric oxide, peroxynitrite and nitroxyl anion, Free Radic. Biol. Med. 25 (1998) 1057–1065;

263) O'Malley D.M., Whetten R., Bao W., Chen C.L., Sederoff R.R., The role of of laccase in lignification, Plant J. 4 (1993) 751–757;

264) Osawa T., Shibamoto T., Analysis of free malonaldehyde formed in lipid peroxidation systems via a pyrimidine derivative, J. Am. Oil Chem. Soc. 69 (1992) 466-468;

265) Osiadacz J., Adhami A.J.H., Bjraszewska D., Fischer P., Peczyniska C.W., On the use of Trametes versicolor laccase for the conversion of 4-methyl-3-hydroxyanthranilic acid to actinocin chromophore, J. Biotechnol. 72 (1999) 141–149;

266) Osma J.F., Saravia V., Herrera J.L.T., Couto S. R., Mandarin peelings: The best carbon source to produce laccase by static cultures of Trametes pubescens, Chemosphere 67 (2007) 1677–1680;

267) Ozcelik B., Lee J.H., Min D.B. Effects of light, oxygen, and pH on the absorbance of 2,2-diphenyl-1-picrylhydrazyl, J. Food Sci. 68 (2003) 487-490;

268) Paganga G., Rice-Evans C.A., The identification of flavonoids as glycosides in human plasma, FEBS Lett. 401 (1997) 78–82;

269) Palmer A.E., Szilagyi R.K., Cherry J.R., Jones A., Xu F., Solomon E.I., Spectroscopic characterization of the Leu513His variant of fungal laccase: effect of increased axial ligand interaction on the geometric and electronic structure of the type I copper site, Inorg. Chem. 42 (2003) 4006-4017;

270) Palmer A.E., Randall D.W., Xu F., Solomon E.I., Spectroscopic studies and electronic structure description of the high potential type 1 copper site in fungal laccase: Insight into the effect of the axial ligand, J. Am. Chem. Soc. 121 (1999) 7138–7149;

271) Palmieri G., Cennamo G., Faraco V., Amoresano A., Sannia G., Giardina P., Atypical laccase isoenzymes from copper supplemented Pleurotus ostreatus cultures, Enzyme. Microb. Technol. 33 (2003) 220–230;

272) Palmieri G., Giardina P., Bianco C., Scaloni A., Capasso A., Sannia G., A novel white laccase from Pleurotus ostreatus, J. Biol. Chem. 272 (1997) 31301–31307;

273) Palonen H., Saloheimo M., Viikari L., Kruus K., Purification, characterization and sequence analysis of a laccase from the ascomycete Mauginiella sp., Enzyme Microb. Technol. 33 (2003) 854–862;

274) Pârvu M., Pârvu A.E., Antifungal plant extracts. In: Science against microbial pathogens: communicating current research and technological advances, A Méndez-Vilas (Ed.) (2011) p. 1055-1062.

275) Pârvu M., Pârvu A.E., Crăciun C., Barbu-Tudoran L., Tămaş M., Antifungal activities of Chelidonium majus extract on Botrytis cinerea in vitro and ultrastructural changes in its conidia, J. Phytopathol. 156 (2008) 550–552;

276) Pena R.C., Propolis standardization: a chemical and biological review, Cien. Invest. Agr., 35 (2008) 11-20;

277) Pereira L., Coelhoa A.V., Viegas C.A., Santos M.M.C., Robalo M.P., Martins L.O., Enzymatic biotransformation of the azo dye Sudan Orange G with bacterial CotA-laccase, J. Biotechnol. 139 (2009) 68–77;

278) Pereira P., Bastos C., Tzanov T., Cavaco-Paulo A., Guebitz G.M., Environmentally friendly bleaching of cotton using laccases, Environ. Chem. Lett. 3 (2005) 66–69;

279) Periasamy R., Palvannan T., Optimization of laccase production by Pleurotus ostreatus IMI 395545 using the Taguchi DOE methodology, J. Basic Microbiol. 50 (2010) 548-556;

280) Pezet R., Pont V., Hoang-Van K., Evidence for oxidative detoxication of pterostilbene and resveratrol by a laccase-like stilbene oxidase produced by Botrytis cinerea, Physiol. Mol. Plant Pathol. 39 (1991) 441–450;

281) Pezet R., Pont V., Hoang-Van K., Enzymatic detoxication of stilbenes by Botrytis cinerea and inhibition by grape berries proanthrocyanidins. In: Verhoeff K., Malathrakis N.E., Williamson B., (eds), Recent Advances in Botrytis Research, Pudoc Scientific, Wageningen, (1992) p. 87–92;

282) Pezet R., Purification and characterization of a 32-kDa laccase-like stilbene oxidase produced by Botrytis cinerea, FEMS Microbiol. Lett. 167 (1998) 203–208;

283) Piontek K., Antorini M., Choinowski T., Crystal structure of a laccase from the fungus Trametes versicolor at 1.90-Å resolution containing a full complement of coppers, J. Biol. Chem. 277 (2002) 37663–37669;

284) Piscitelli A., Giardina P., Lettera V., Pezzella C., Sannia G., Faraco V., Induction and transcriptional regulation of laccases in fungi, Curr. Genet. 12 (2011) 104-112;

285) Popova T.V., Aksenova N.V., Complexes of copper in unstable oxidation states, Russ. J. Coord. Chem. 29 (2003) 743-745;

286) Popp R., Schimmer O., Induction of sister-chromatid exchanges (SCE), polyploidy, and micronuclei by plant flavonoids in human lymphocyte cultures. A comparative study of 19 flavonoids, Mutat. Res. 246 (1991) 205–213;

287) Pozdnyakova N., Rodakiewicz-Nowak J., Turkovskaya O.V., Haber J., Oxidative degradation of polyaromatic hydrocarbons and their derivatives catalyzed directly by the yellow laccase from Pleurotus ostreatus D1, J. Mol. Catal. B: Enzym. 41 (2006) 8-15;

288) Pozdnyakova N.N., Rodakiewicz-Nowak J., Turkovskaya O.V., Catalytic properties of yellow laccase from Pleurotus ostreatus D1, J. Mol. Catal. B: Enzym. 30 (2004) 19–24;

289) Pozdnyakova N.N., Turkovskaya O.V., Yudina E.N., Rodakiewicz-Nowak J., Yellow laccase from the fungus Pleurotus ostreatus D1: purification and characterization, Appl. Biochem. Microbiol. 42 (2006) 56–61;

290) Prior R.L., Wu X., Schaich K., Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements, J. Agric. Food Chem. 53 (2005) 4290–4302;

291) Procházková D., Boušová I., Wilhelmová N., Antioxidant and prooxidant properties of flavonoids, Fitoterapia. 82 (2011) 513–523;

292) Prytzyk E., Dantas A.P., Salomao K., Pereira A.S., Bankova V.S., De Castro S.L., Aquino Neto F.R., Flavonoids and trypanocidal activity of Bulgarian propolis, J. Ethnopharmacol., 88 (2003) 189-193;

293) Purdy L.H., Sclerotinia sclerotiorum: history, diseases and symptomatology, host range, geographic distribution, and impact, Phytopathology 69 (1979) 875-880;

294) Quintanar L., Stoj C., Taylor A.B., Hart P.J., Kosman D.J., Solomon E.I., Shall we dance? How a multicopper oxidase chooses its electron transfer partner, Acc. Chem. Res. 40 (2007) 445-452;

295) Quintanar L., Stoj C., Wang T.P., Kosman D.J., Solomon E.I., Role of aspartate 94 in the decay of the peroxide intermediate in the multicopper oxidase Fet3p, Biochemistry 44 (2005) 6081–6091;

296) Raaman N, Phytochemical Techniques, New India Publishing Agency, New Delhi, India (2006);

297) Randall D.W., DeBeer George S. Hedman B., Hodgson K.O., Fujisawa K., Solomon E.I., Spectroscopic and rlectronic structural studies of blue copper model complexes. 1. perturbation of the thiolate−Cu bond, J. Am. Chem. Soc. 122 (2000) 11620-11631

298) Randall D.W., DeBeer George S., Holland P.L., Hedman B., Hodgson K.O., Tolman W.B., Solomon E.I., Spectroscopic and electronic structural studies of blue copper model complexes. 2. comparison of three- and four-coordinate Cu(II)−thiolate complexes and fungal laccase, J. Am. Chem. Soc. 122 (2000) 11632-11648

299) Ranocha P., McDougall G., Hawkins S., Sterjiades R., Borderies G., Stewart D., Cabanes-Macheteau M., Boudet A.M., Goffner D., Biochemical characterization, molecular cloning and expression of laccases—a divergent gene family—in poplar, Eur. J. Biochem. 259 (1999) 485–495;

300) Reeder B.J., Grey M., Silaghi-Dumitrescu R.L., Svistunenko D.A., Bulow L., Cooper C.E., Tyrosine residues as redox cofactors in human hemoglobin: implications for engineering nontoxic blood substitutes, J. Biol. Chem. 283 (2008) 30780-30787;

301) Reeder B.J., Svistunenko D.A., Cooper C.E., Wilson M.T., The radical and redox chemistry of myoglobin and hemoglobin: from in vitro studies to human pathology, Antioxid. Redox Sign. 6 (2004) 954-966;

302) Reeder B.J., Svistunenko D.A., Sharpe M.A., Wilson M.T., Characteristics and mechanism of formation of peroxide-induced heme to protein cross-Linking in myoglobin, Biochemistry 41 (2002) 367-375;

303) Reinhammar B.R.M., Oxidation–reduction potentials of the electron acceptors in laccases and stellacyanin, Biochim. Biophys. Acta 275 (1972) 245–259;

304) Rice-Evans C.A., Miller N.J., Paganga G., Structure–antioxidant activity relationships of flavonoids and phenolic acids, Free Radic. Biol. Med. 20 (1996) 933–956;

305) Rifkind J.M., Nagababu E., Ramasamy S., Ravi L.B., Hemoglobin redox reactions and oxidative stress, Redox Rep. 8 (2003) 234-237;

306) Rigling D., Alfen N.K.V., Extra and intracellular laccases of the chestnut blight fungus, Cryphonectria parasitica, Appl. Environ. Microbiol. 59 (1993) 3634–3639;

307) Roberts S.A., Weichsel A., Grass G., Thakali K., Hazzard J.T., Tollin G., Rensing C., Montfort W.R., Crystal structure and electron transfer kinetics of CueO, a multicopper oxidase required for copper homeostasis in Escherichia coli, Proc. Natl. Acad. Sci. USA 99 (2002) 2766–2771;

308) Robles A., Lucas R., Martinez-Canamero M., Omar N.B., Perez R., Galvez A., Characterisation of laccase activity produced by the hyphomycete Chalara (syn. Thielaviopsis) paradoxa CH32, Enzyme Microb. Technol. 31 (2002) 516–22;

309) Rodakiewicz-Nowak J., Haber J., Pozdnyakova N., Leontievsky A., Golovleva L.A., Effect of ethanol on enzymatic activity of fungal laccases, Bioscience Rep. 19 (1999) 589-600;

310) Rodgers C.J., Blanford C.F., Giddens S.R., Skamnioti P., Armstrong F.A., Gurr S.J., Designer laccases: a vogue for high-potential fungal enzymes?, Trends Biotechnol. 28 (2009) 63-72;

311) Rollins J.A., The Sclerotinia sclerotiorum pac1 gene is required for sclerotial development and virulence, Mol. Plant Microbe Inter.16 (2003) 785-795;

312) Rollins J.A., Dickman M.B., pH signaling in Sclerotinia sclerotiorum: identification of a pacC/RIM1 homolog, Appl. Envir. Microbiol. 67 (2001) 75–81;

313) Rosconi F., Fraguas L.F., Martinez-Drets G., Castro-Sowinski S., Purification and characterization of a periplasmic laccase produced by Sinorhizobium meliloti, Enzyme Microb. Technol. 36 (2005) 800–807;

314) Ryden L.G., Hunt L.T., Evolution of protein complexity: The blue copper-containing oxidases and related proteins, J. Mol. Evol. 36 (1993) 41–66;

315) Sadhasivam S., Savitha S., Swaminathan K., Lin F.H.L, Production, purification and characterization of mid-redox potential laccase from a newly isolated Trichoderma harzianum WL1, Process Biochem. 43 (2008) 736–742;

316) Sahu S.C., Gray G.C., Kaempferol-induced nuclear DNA damage and lipid peroxidation, Cancer Lett. 85 (1994) 159–164;

317) Saija A., Scalese M., Lanza M., Marzullo D., Bonina F., Castelli F., Flavonoids as antioxidant agents: importance of their interaction with biomembranes, Free Radic. Biol. Med. 19 (1995) 481-486;

318) Sakurai T., Kataoka K., Structure and function of type I copper in multicopper oxidases, Cell. Mol. Life Sci. 64 (2007) 2642-2656;

319) Salatino A., Teixeira E.W., Negri G., Message D., Origin and Chemical Variation of Brazilian Propolis, Evid. Comp. Alt. Med. 2 (2005) 33-38;

320) Sanchez-Amat A., Lucas-Elio P., Fernandez E., Garcia-Borron J.C., Solano F., Molecular cloning and functional characterization of a unique multipotent polyphenol oxidase from Marinomonas mediterranea, Biochim. Biophys. Acta 1547 (2001) 104–116;

321) Santos M.R., Rodríguez-Goméz M.J., Justino G.C., Charro N., Florencio M.H., Miral L., Influence of the metabolic profile on the in vivo antioxidant activity of quercetin under a low dosage oral regimen in rats, Br. J. Pharmacol. 153 (2008) 1750–1761;

322) Sârbu, C., Pop H., Principal component analysis versus fuzzy principal component analysis. A case study: the quality of Danube water (1985–1996), Talanta 65 (2005) 1215–1220;

323) Sârbu C., Moţ A.C., Ecosystem discrimination and fingerprinting of Romanian propolis by hierarchical fuzzy clustering and image analysis of TLC patterns, Talanta 85 (2011) 1112-1117;

324) Sato H., Koyama S., Patent number JP 149235 (2006);

325) Sato Y., Wuli B., Sederoff R., Whetten R., Molecular cloning and expression of eight cDNAs in loblolly pine (Pinus taeda), J. Plant Res. 114 (2001) 147–155;

326) Schauss A.G., Wu X., Prior R.L., Ou B., Huang D., Owens J., Agarwal A., Jensen G.S., Hart A.N., Shanbrom E., Antioxidant Capacity and Other Bioactivities of the Freeze-Dried Amazonian Palm Berry, Euterpe oleraceae Mart. (Acai), J. Agr. Food Chem. 54 (2006) 8604-8610;

327) Selinheimo E., Autio K., Kruus K., Buchert J., Elucidating the mechanism of laccase and tyrosinase in wheat bread making, J. Agr. Food Chem. 55 (2007) 6357–6365;

328) Selinheimo E., Kruus K., Buchert J., Hopia A., Autio K., Effects of laccase, xylanase and their combination on the rheological properties of wheat doughs, J. Cer. Sci. 43 (2006) 152-159;

329) Serpen A., Capuano E., Fogliano V., Gökmen V., A new procedure to measure the antioxidant activity of insoluble food components, J. Agr. Food Chem. 55 (2007) 7676-7681;

330) Servili M., DeStefano G., Piacquadio P., Sciancalepore V., A novel method for removing phenols from grape must, Am. J. Enol. Vitic. 51 (2000) 357–361;

331) Setti L., Giuliani S., Spinozzi G., Pifferi P.G., Laccase catalyzedoxidative coupling of 3-methyl 2-benzothiazolinone hydrazone and methoxyphenols, Enzyme Microbiol. Technol. 25 (1999) 285–289;

332) Sharma K.K., Kuhad R.C., Laccase: enzyme revisited and function redefined, Indian J. Microbiol. 48 (2008) 309–316;

333) Shin K.S., Lee Y.J., Purification and characterization of a new member of the laccase family from the white-rot basidiomycete Coriolus hirsutus, Arch. Biochem. Biophys., 384 (2000) 109–115;

334) Shin W., Sundaram U.M., Cole J.L., Zhang H.M., Hedman B., Hodgson K.O., Solomon E.I., Chemical and spectroscopic definition of the peroxide-level intermediate in the multicopper oxidases: relevance to the catalytic mechanism of dioxygen reduction to water, J. Am. Chem. Soc. 118 (1996) 3202–3215;

335) Shleev S., Nikitina O., Christenson A., Reimann C.T., Yaropolov A.I., Ruzgas T., Gorton L., Characterization of two new multiforms of Trametes pubescens laccase, Bioorg. Chem. 35 (2007) 35-49;

336) Shleev S., Tkac J., Christenson A., Ruzgas T., Yaropolov A.I., Whittaker J.W., Gorton L., Direct electron transfer between copper-containing proteins and electrodes, Biosens. Bioel. 20 (2005) 2517–2554;

337) Shleev S.V., Morozova O.V., Nikitina O.V., Gorshina E.S., Rusinova T.V., Serezhenkov V.A., Burbaev D.S., Gazaryan I.G., Yaropolov A.I., Comparison of physico-chemical characteristics of four laccases from different basidiomycetes, Biochimie 86 (2004) 693–703;

338) Shleev S.V., Reimann C.T., Serezhenkov V., Burbaev D., Yaropolov A.I., Gorton L., Ruzgas T., Autoreduction and aggregation of fungal laccase in solution phase: possible correlation with a resting form of laccase, Biochimie 88 (2006) 1275–1285;

339) Shraddha R., Shekher R., Sehgal S., Kamthania M., Kumar A., Laccase: microbial sources, production, purification, and potential biotechnological applications, Enzyme Res. (2011) ID 217861, pages 11;

340) Silaghi-Dumitrescu R., Reeder B.J., Nicholls P., Cooper C.E., Wilson M.T., Ferryl haem protonation gates peroxidatic reactivity in globins, Biochem. J. 403 (2007) 391-5;

341) Silaghi-Dumitrescu R., Horseradish peroxidase - a versatile catalyst. Horseradish peroxidase - a versatile catalyst, Research Signpost, India (2006);

342) Silaghi-Dumitrescu R., High-valent metalloporphyrins in hydrocarbon activation: metal(V)-oxo or metal(V)-hydroxo?, New J. Chem. 34 (2010) 1830-1833;

343) Silaghi-Dumitrescu R., Silaghi-Dumitrescu I., DFT and the electromerism in complexes of iron with diatomic ligands, J. Inorg. Biochem. 100 (2006) 161-166;

344) Silaghi-Dumitrescu R., Dioxygen activation by Rieske dioxygenases –computational studies. 1. Possible catalytic intermediates, Stud. U. Babes-Bol. Che. 2 (2007) 103-127;

345) Silaghi-Dumitrescu R., Makarov S.V., A computational analysis of electromerism in hemoprotein Fe(I) models, J. Biol. Inorg. Chem. 15 (2010) 977-86;

346) Simkus R.A., Laurinavicius V., Boguslavsky L., Skotheim T., Tanenbaum S., Nakas J.P., Slomczynski D.J., Laccase containing sol-gel based optical biosensors, Anal. Lett. 29 (1996) 1907-1919;

347) Singleton V.L., Rossi Jr. J.A., Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents, Am. J. Enol. Vitic. 16 (1965) 144-158;

348) Skálová T., Dohnálek J., Østergaard L.H., Østergaard P.R., Dušková J., Štěpánková A., Hašek J, The structure of the small laccase from Streptomyces coelicolor reveals a link between laccases and nitrite reductases, J. Mol. Biol. 385 (2009) 1165–1178;

349) Smith P.F., Langworthy T.A., Smith M.R., Polypeptide nature of growth requirement in yeast extract for Thermoplasma acidophilum, J. Bacteriol. 124 (1975) 884-892;

350) Soares G.M.B., Costa F.M., Amorium M.T.P, Decolorization of an anthraquinone-type dye using a laccase formulation, Biores. Technol. 79 (2001) 171–177;

351) Soden D.M., Dobson A.D., Differential regulation of laccase gene expression in Pleurotus sajor-caju, Microbiology 147 (2001) 1755–1763;

352) Solomon E.I., Chen P., Metz M., Lee S.K., Palmer A.E., Oxygen binding, activation, and reduction to water by copper proteins, Angew. Chem. Int. Ed. Engl., 40 (2001) 4570-4590;

353) Solomon E.I., Szilagyi R.K., George S.D., Basumallick L., Electronic structures of metal sites in proteins and models: contributions to function in blue copper proteins, Chem. Rev. 104 (2004) 419–458;

354) Solomon E.I., Sundaram U.M., Machonkin T.E., Multicopper oxidases and oxygenases, Chem. Rev. 96 (1996) 2563–2605;

355) Solomon E.I., Augustine, A.J., Yoon J., Oxygen reduction to water by the multicopper oxidases, Dalton Trans. 14 (2008) 3921–3932;

356) Solomon E.I., Decker A., Lehnert N., Non-heme iron enzymes: contrasts to heme catalysis, Proc. Natl. Acad. Sci. USA 100 (2003) 3589-3594;

357) Song Y., Buettner G.R., Parkin S., Wagner B.A., Robertson L.W., Lehmler H.J., Chlorination increases the persistence of semiquinone free radicals derived from polychlorinated biphenyl hydroquinones and quinones, J. Org. Chem. 73 (2008) 8296-8304;

358) Song Y., Wagner B.A., Lehmler H.J., Buettner G.R., Semiquinone radicals from oxygenated polychlorinated biphenyls: electron paramagnetic resonance studies, Chem. Res. Toxicol. 21 (2008) 1359-1367;

359) Song Y., Wagner B.A., Witmer J.R., Lehmler H.J., Buettner G.R., Nonenzymatic displacement of chlorine and formation of free radicals upon the reaction of glutathione with PCB quinones, Proc. Natl. Acad. Sci. USA 106 (2009) 9725-9730;

360) Srnec M., Ryde U., Rulisek L., Reductive cleavage of the O-O bond in multicopper oxidases: a QM/MM and QM study, Faraday Discuss. 148 (2011) 41–53;

361) StatSoft (2010). Retrived July 1, (2010) from: www.statsoft.com

362) Steinmetz K.A., Potter J.D., Vegetables, fruit, and cancer prevention: a review, J. Am. Diet. Assoc. 96 (1996,) 1027– 1039;

363) Sterjiades R., Dean J.F.D., Eriksson K.E.L., Laccase from Sycamore Maple (Acer pseudoplatanus) polymerizes monolignols, Plant Physiology 99 (1992) 1162-1168;

364) Strong P.J., Claus H., Laccase: a review of its past and its future in bioremediation, Critical Rev. Envir. Sci. Technol. 41 (2011) 373-434;

365) Sun F., Hayami S., Haruna S., Ogiri Y., Tanaka K., Yamada Y., Ikeda K., Yamada H., Sugimoto H., Kawai N., Kojo S., In vivo antioxidative activity of propolis evaluated by the interaction with vitamin C and vitamin E and the level of lipid hydroperoxides in rats, J. Agr. Food Chem., 48 (2000) 1462–1465;

366) Sundberg A., Holmbom B., Willf S., Pranovich A., Weakening of paper strength by wood resin, Nordic Pulp Paper Res. J. 15 (2000) 46–53;

367) Suzuki T., Endo K., Ito M., Tsujibo H., Miyamoto K., Inamori Y., A thermostable laccase from Streptomyces lavendulae REN-7: purification, characterization, nucleotide sequence, and expression, Biosci. Biotechnol. Biochem. 67 (2003) 2167–2175;

368) Svistunenko D.A., Reaction of haem containing proteins and enzymes with hydroperoxides: the radical view, Biochim. Biophys. Acta 1707 (2005) 127-155;

369) Tadesse M.A., D’Annibale A., Galli C., Gentilia P., Sergia F., An assessment of the relative contributions of redox and steric issues to laccase specificity towards putative substrates, Org. Biomol. Chem. 6 (2008) 868–878;

370) Tanaka T., Nose M., Endo A., Fujii T., Taniguki M., Treatment of nonylphenol with laccase in a rotating reactor, J. Biosci. Bioeng. 96 (2004) 541-546;

371) Tarantilis P.A., Troianou V.E., Pappasa C.S., Kotseridisb Y.S., Polissioua M.G., Differentiation of Greek red wines on the basis of grape variety using attenuated total reflectance Fourier transform infrared spectroscopy, Food Chem. 1 (2008) 192-196;

372) Teixeira E.W., Message D., Negri G., Salatino A., Stringheta P.C. Seasonal variation, chemical composition and antioxidant activity of Brazilian propolis samples, Evid. Compl. Alt. Med.31 (2008) 1-9;

373) Tezuka K., Hayashi M., Ishikara H., Onozaki K., Nishimura M., Takahashi N., Occurrence of heterogeneity on N-linked oligosaccharides attached to sycamore (Acer pseudoplatanus L.) laccase of excretion, Biochem. Mol. Biol. Int. 29 (1993) 395–402;

374) Thaipong K., Boonprako U., Crosby K., Cisneros-Zevallos L., Byrne D.H., Comparison of ABTS, DPPH, FRAP, and ORAC assays for estimating antioxidant activity from guava fruit extracts, J. Food Comp. Anal. 19 (2006) 669-675;

375) Thuesen M.H., Farver O., Reinhammar B., Ulstrup J., Cyclicv voltammetry ande electrocatalysis of the blue. copper oxidase polyporus versicolor, Acta Chem. Scand. 52 (1998) 555–562;

376) Thurston C.F., The structure and function of fungal laccases, Microbiology 140 (1994) 19-26;

377) Tijburg L.B.M., Mattern T., Folts J.D., Weisgerber U.M., Katan M.B., Tea flavonoids and cardiovascular diseases: a review, Crit. Rev. Food Sci. Nutr. 37 (1997) 771–785;

378) Torres J., Svistunenko D., Karlsson B., Cooper C.E., Wilson M.T., Fast reduction of a copper center in laccase by nitric oxide and formation of a peroxide intermediate, J. Am. Chem. Soc., 124 (2002) 963–967;

379) Torres-Duarte C., Roman R., Tinoco R., Vazquez-Duhalt R., Halogenated pesticide transformation by a laccase–mediator system, Chemosphere 77 (2009) 687–692;

380) Tosi E.A., Re E., Ortega M.E., Cazzoli A.F., Food preservative based on propolis: Bacteriostatic activity of propolis polyphenols and flavonoids upon Escherichia coli, Food Chem., 104 (2007) 1025-1029;

381) Tsuchiya R., Petersen B.R., Christensen S., patent number US 6074631 (2000);

382) van Acker S.A., Tromp M.N., Haenen G.R., van der Vijgh W.J., Bast A., Flavonoids as scavengers of nitric oxide radical, Biochem. Biophys. Res. Commun. 214 (1995) 755–759;

383) Veluchamy S., Williams B., Kim K., Dickman M.B., The CuZn superoxide dismutase from Sclerotinia sclerotiorum is involved with oxidative stress tolerance, virulence, and oxalate production, Physiol. Mol. Plant Pathol. 78 (2012) 14–23;

384) Verma M., Brar S.K., Tyagi R.D., Sahai V., Prévost D., Valéro J.R., Surampalli R.Y., Bench-scale fermentation of Trichoderma viride on wastewater sludge: Rheology, lytic enzymes and biocontrol activity, Enzyme Microbiol. Technol. 41 (2007) 764–771;

385) Vikineswary S., Abdullah N., Renuvathani M., Sekaran M., Pandey A., Jones E.B.G., Productivity of laccase in solid substrate fermentation of selected agroresidues by Pycnoporus sanguineus, Bioresour. Technol. 97 (2006) 171–177;

386) Villano D., Fernandez-Pachon M.S., Moya M.L., Troncoso A.M., Garcıa-Parrilla M.C., Radical scavenging ability of polyphenolic compounds towards DPPH free radical, Talanta 71 (2007) 230-235;

387) Vollaard N.B., Reeder B.J., Shearman J.P., Menu P., Wilson M.T., Cooper C.E., A new sensitive assay reveals that hemoglobin is oxidatively modified in vivo, Free Radic. Biol. Med. 39 (2005) 1216-1228;

388) Vollaard N.B., Shearman J.P., Cooper C.E., Exercise-induced oxidative stress: myths, realities and physiological relevance, Sports Med. 35 (2005) 1045-1062;

389) Vries O.M.H., Kooistra W.H.C.F., Wessels G.H., Formation of an extracellular laccase by Schizophyllum commune dikaryon, J. Gen. Microbiol. 132 (1986) 2817–2826;

390) Wahleithner J.A., Xu F., Brown K.M., Brown S.H., Golightly E.J., Halkier T., Kauppinen S., Pederson A., Schneider P, The identification and characterization of four laccases from the plant pathogenic fungus Rhizoctonia solani, Curr. Genet. 29 (1996) 395–403;

391) Wallner B., Elofsson A., Can correct protein models be identified?, Protein Sci. 12 (2003) 1073-1086;

392) Wang H.X., Ng T.B., Purification of a novel low molecular mass laccase with HIV-1 reverse transcriptase inhibitory activity from the mushroom Tricholoma giganteum, Biochem. Biophys. Res. Commun. 315 (2004) 450–454;

393) Wang H.X., Ng T.B., Purification of a laccase from fruiting bodies of the mushroom Pleurotus eryngii, Appl. Microbiol. Biotechnol. 69 (2006) 521–525;

394) Widsten P., Kandelbauer A., Laccase applications in the forest products industry: A review, Enzyme Microb. Technol. 42 (2008) 293–307;

395) Williams R.J.P., Energised (entatic) states of groups and of secondary structures in proteins and metalloproteins, Eur. J. Biochem. 234 (1995) 363-381;

396) Williamson P.R., Biochemical and molecular characterization of the diphenol oxidase of Cryptococcus neoformans: identification as a laccase, J. Bacteriol. 176 (1996) 656–664;

397) Wilms L.C., Kleinjans J.C., Moonen E.J., Briede J.J., Discriminative protection against hydroxyl and superoxide anion radicals by quercetin in human leucocytes in vitro, Toxicol. In Vitro 22 (2008) 301–307;

398) Wong A.L., Willetts H.J., Polyacrylamide-gel electrophoresis of enzymes during morphogenesis of Sclerotia of Sclerotinia sclerotiorum, J. Gen. Microbiol. 81 (1974) 101–109;

399) Wood D.A., Production, purification and properties of extracellular laccase of Agaricus bisporus, J. Gen. Microbiol. 117 (1980) 327–338;

400) Wood D.A., Production, purification and properties of extracellular laccase of Agaricus bisporus, J. Gen. Microbiol. 117 (1980) 327–338;

401) Worrall J.J., Chet I., Huttermann A., Association of Rhizomorph Formation with Laccase Activity in Armillaria spp., J. Gen. Appl. Microbiol. 132 (1986) 2527-2533;

402) Wu Y.W., Sun S.Q., Zhao J., Li Y., Zhou Q., Rapid discrimination of extracts of Chinese propolis and poplar buds by FT-IR and 2D IR correlation spectroscopy, J. Mol. Struct. 883 (2008) 48–54;

403) Wu Y.R., Luo Z.H., Kwok-Kei R., Vrijmoed C.L.L.P., Purification and characterization of an extracellular laccase from an anthracenedegrading fungus Fusarium solani MAS2, Bioresour. Technol. 101 (2010) 9772-9777;

404) Wynn R.M., Sarkar H.K., Holwerda R.A., Knaff D.B., Fluorescence associated with the type 3 copper center of laccase, FEBS Lett. 156 (1983) 23-28;

405) Xu F., Berka R.M., Waheithner J.A., Nelson B.A., Shuster J.R., Brown S.H., Palmer A.E., Solomon E.I., Site-directed mutations in fungal laccase: effect on redox potential, activity and pH profile, Biochem. J. 334 (1998) 63-70;

406) Xu F., Oxidation of phenols, anilines, and benzenethiols by fungal laccases: correlation between activity and redox potentials as well as halide inhibition, Biochemistry 35 (1996) 7608–7614;

407) Xu F., Palmer A.E., Yaver D.S., Berka R.M., Gambetta G.A., Brown S.H., Solomon E.I., Targeted mutations in a Trametes villosa laccase, J. Biol. Chem., 274 (1999) 12372–12375;

408) Xu F., Shin W., Brown S.H., Wahleitner J.A., Sundaram U.M., Solomon E.I., A study of recombinant fungal laccases and bilirubin oxidase that exhibit significant differences in redox potential, substrate specificity, and stability, Biochim. Biophys. Acta 1292 (1996) 303–311;

409) Yamashita N., Tanemura H., Kawanishi S., Mechanism of oxidative DNA damage induced by quercetin in the presence of Cu(II), Mutat. Res. 425 (1999) 107–115;

410) Yaropolov A.I., Skorobogatko O.V., Vartanov S.S., Varfolomeev S.D., Laccase: properties, catalytic mechanism, and applicability, Appl. Biochem. Biotechnol., 49 (1994) 257–280;

411) Yaver D.S., Xu F., Golightly E.J., Brown K.M., Brown S.H., Rey M.W., Schneider P., Halkier T., Mondorf K., Dalboge H., Purification, characterization, molecular cloning, and expression of two laccase genes from the white rot basidiomycete Trametes villosa, Appl. Environ. Microbiol. 62 (1996) 834–841;

412) Yen G.C., Duh P.D., Tsai H.L., Huang S.L., Pro-oxidative properties of flavonoids in human lymphocytes, Biosci. Biotechnol. Biochem. 67 (2003) 1215–1222;

413) Yoon J., Liboiron B.D., Sarangi R., Hodgson K.O., Hedman B., Solomon E.I., The two oxidized forms of the trinuclear Cu cluster in the multicopper oxidases and mechanism for the decay of the native intermediate, Proc. Natl. Acad. Sci. USA 104 (2007) 13609-13614;

414) Yoon J., Solomon E.I., Electronic structure of the peroxy intermediate and its correlation to the native intermediate in the multicopper oxidases: insights into the reductive cleavage of the O–O bond, J. Am. Chem. Soc. 129 (2007) 13127–13136;

415) Yoon J., Fujii S., Solomon E.I., Geometric and electronic structure differences between the type 3 copper sites of the multicopper oxidases and hemocyanin/tyrosinase, Proc. Natl. Acad. Sci. USA, 106 (2009) 6585–6590;

416) Yoshida H., Chemistry of lacquer (urushi), J. Chem. Soc. 43 (1883) 472–486;

417) Yoshizawa K., Kihara N., Kamachi T., Shiota Y., Catalytic mechanism of dopamine β-monooxygenase mediated by Cu(III)-oxo, Inorg. Chem. 45 (2006) 3034-3041;

418) Zhang G.Q., Wang Y.F., Zhang X.Q., Ng T.B., Wang H.X., Purification and characterization of a novel laccase from the edible mushroom Clitocybe maxima, Process Biochem. 45 (2010) 627–633;

419) Zhang H.Y., Structure-Activity relationships and rational design strategies for radical-scavenging antioxidants, Curr. Comput. Aided. Drug Des. 1 (2005) 257-273;

420) Zhang X., Eigendorf G., Stebbing D.W., Mansfield S.D., Saddler J.N., Degradation of trilinolein by laccase enzymes, Arch. Biochem. Biophys. 405 (2002) 44–54;

421) Zhao C., Shi Y., Lin W., Wang W., Jia Z., Yao S., Fan B., Zheng R., Fast repair of the radical cations of dCMP and poly C by quercetin and rutin, Mutagenesis 16 (2001) 271-275;

422) Zhoua Y., Deng T., Pana C., Chen C., Mo J., Purification of a laccase from fungus combs in the nest of Odontotermes formosanus, Process Biochem. 45 (2010) 1052–1056;

423) Zhu X., Gibbons J., Garcia-Rivera J., Casadevall A., Williamson P.R., Laccase of Cryptococcus neoformans is a cell wall-associated virulence factor, Infect. Immun. 69 (2001) 5589–5596;

424) Zhukova Y.N., Zhukhlistova N.E., Lyashenko A.V., Morgunova E.Y., Zaitsev V.N., Mikhaoelov A.M., Comparative Analysis of Spatial Organization of Laccases from Cerrena maxima and Coriolus zonatus, Kristallografiya 52 (2007) 854–865;

425) Zouari-Mechichi H., Mechichi T., Dhouib A., Sayadi S., Martinez A.T., Martinez M., Laccase purification and characterization from Trametes trogii isolated in Tunisia: Decolorization of textile dyes by the purified enzyme, Enzyme. Microb. Technol. 39 (2006) 141–148;

List of personal publications on thesis topic at 03^rd October 2012

1. Moţ A.C., Damian G., Sarbu C., Silaghi-Dumitrescu R., Redox reactivity in propolis: direct detection of free radicals in basic medium and interaction with hemoglobin, Redox Report 14 (2009) 267-274; (IF: 1.732)

2. Moţ A.C., Silaghi-Dumitrescu R., Sarbu C., Rapid and effective evaluation of the antioxidant capacity of propolis extracts using DPPH bleaching kinetic profiles, FT-IR and UV–vis spectroscopic data, Journal of Food Composition and Analysis 24 (2011) 516–522; (IF: 2.079)

3. Lupan A., Matyas C., Moţ A.C., Silaghi-Dumitrescu R., Can geometrical distortions make a laccase change color from blue to yellow?, Studia Universitatis Babes-Bolyai Chemia, 56 (2011) 231-238. (IF: 0.129)

4. Moţ A.C., Pârvu M., Damian G., Irimie F.D., Darula Z., Medzihradszky K.F., Brem B., Silaghi-Dumitrescu R., A “yellow” laccase with “blue” spectroscopic features, from Sclerotinia sclerotiorum, Process Biochemistry 47 (2012) 968–975; (IF: 2.627)

5. Moţ A.C., Syrbu S.A., Makarov S.V., Damian D., Silaghi-Dumitrescu R., Axial ligation in water-soluble copper porphyrinates: contrasts between EPR and UV–vis, Inorganic Chemistry Communications 18 (2012) 1-3; (IF: 1.972)

6. Imre A., Moţ A.C., Silaghi-Dumitrescu R., Exploring the possibility of high-valent copper in models of copper proteins with a three-histidine copper-binding motif, Central European Journal of Chemistry 10 (2012) 1527-1533; (IF: 1.073)

7. Moţ A.C., Silaghi-Dumitrescu R., Laccases: complex architectures for one-electron oxidations, Biochemistry (Moscow), accepted; (IF: 1.058)

General conclusions

List of personal publications on thesis topic at 03rd October 2012

List of personal publications on thesis topic at 03^rd October 2012