Discovery of peptides with saltiness-enhancing effects in enzymatic hydrolyzed Agaricus bisporus protein and evaluation of their salt-reduction property.

This study aimed to screen peptides with saltiness-enhancing effects from enzymatic hydrolyzed Agaricus bisporus protein and quantify their salt-reduction. The saltiness evaluation standard curve was first established to evaluate salinity. The peptide fractions (U-1, U-2, and U-3) were obtained from enzymatic hydrolyzed Agaricus bisporus protein by ultrafiltration. Quantitative calculations showed that the U-2 fraction (200-2000 Da) had the strongest saltiness-enhancing effect, and its perceived saltiness in 50 mmol NaCl solution was 60.24 ± 0.10 mmol/L. The peptide sequences were identified by liquid chromatography/mass spectrometry (LC-MS/MS). Results suggested that the potential peptides with saltiness-enhancing effects were umami peptides. Molecular docking with the umami receptor T1R1/T1R3 revealed that the key amino acid residues were Asp82, Glu392, Glu270, and Asp269. Furthermore, peptide YDPNDPEK (976.4138 Da), DDWDEDAPR(1117.4312 Da), and DVPDGPPPE (1058.4668 Da) were synthesized for salt-reduction quantification. 0.4 % peptide YDPNDPEK in NaCl solution was found to have a salt-reduction of 30 %, which provided the basic theory and data for the salt-reduction of peptide in enzymatic hydrolyzed Agaricus bisporus protein.

Determination of tyrosinase-cyanidin-3-O-glucoside and (-/+)-catechin binding modes reveal mechanistic differences in tyrosinase inhibition.

Tyrosinase, exquisitely catalyzes the phenolic compounds into brown or black pigment, inhibition is used as a treatment for dermatological or neurodegenerative disorders. Natural products, such as cyanidin-3-O-glucoside and (-/+)-catechin, are considered safe and non-toxic food additives in tyrosinase inhibition but their ambiguous inhibitory mechanism against tyrosinase is still elusive. Thus, we presented the mechanistic insights into tyrosinase with cyanidin-3-O-glucoside and (-/+)-catechin using computational simulations and in vitro assessment. Initial molecular docking results predicted ideal docked poses (- 9.346 to - 5.795 kcal/mol) for tyrosinase with selected flavonoids. Furthermore, 100 ns molecular dynamics simulations and post-simulation analysis of docked poses established their stability and oxidation of flavonoids as substrate by tyrosinase. Particularly, metal chelation via catechol group linked with the free 3-OH group on the unconjugated dihydropyran heterocycle chain was elucidated to contribute to tyrosinase inhibition by (-/+)-catechin against cyanidin-3-O-glucoside. Also, predicted binding free energy using molecular mechanics/generalized Born surface area for each docked pose was consistent with in vitro enzyme inhibition for both mushroom and murine tyrosinases. Conclusively, (-/+)-catechin was observed for substantial tyrosinase inhibition and advocated for further investigation for drug development against tyrosinase-associated diseases.

Wells-Dawson phosphotungstates as mushroom tyrosinase inhibitors: a speciation study.

In order to elucidate the active polyoxotungstate (POT) species that inhibit fungal polyphenol oxidase (AbPPO4) in sodium citrate buffer at pH 6.8, four Wells-Dawson phosphotungstates [α/ß-PV2WVI18O62]6- (intact form), [α2-PV2WVI17O61]10- (monolacunary), [PV2WVI15O56]12- (trilacunary) and [H2PV2WVI12O48]12- (hexalacunary) were investigated. The speciation of the POT solutions under the dopachrome assay (50 mM Na-citrate buffer, pH 6.8; L-3,4-dihydroxyphenylalanine as a substrate) conditions were determined by 183W-NMR, 31P-NMR spectroscopy and mass spectrometry. The intact Wells-Dawson POT [α/ß-PV2WVI18O62]6- shows partial (~ 69%) disintegration into the monolacunary [α2-PV2WVI17O61]10- anion with moderate activity (Ki = 9.7 mM). The monolacunary [α2-PV2WVI17O61]10- retains its structural integrity and exhibits the strongest inhibition of AbPPO4 (Ki = 6.5 mM). The trilacunary POT [PV2WVI15O56]12- rearranges to the more stable monolacunary [α2-PV2WVI17O61]10- (~ 62%) accompanied by release of free phosphates and shows the weakest inhibition (Ki = 13.6 mM). The hexalacunary anion [H2PV2WVI12O48]12- undergoes time-dependent hydrolysis resulting in a mixture of [H2PV2WVI12O48]12-, [PV8WVI48O184]40-, [PV2WVI19O69(H2O)]14- and [α2-PV2WVI17O61]10- which together leads to comparable inhibitory activity (Ki = 7.5 mM) after 48 h. For the solutions of [α/ß-PV2WVI18O62]6-, [α2-PV2WVI17O61]10- and [PV2WVI15O56]12- the inhibitory activity is correlated to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The rearrangement of hexalacunary [H2PV2WVI12O48]12- into at least four POTs with a negligible amount of monolacunary anion interferes with the correlation of activity to the degree of their rearrangement to [α2-PV2WVI17O61]10-. The good inhibitory effect of the Wells-Dawson [α2-PV2WVI17O61]10- anion is explained by the low charge density of its protonated forms Hx[α2-PV2WVI17O61](10-x)- (x = 3 or 4) at pH 6.8.

Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects.

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC50 =0.18 µM) that proved to be ∼100-fold more active than reference compound kojic acid (IC50 =17.76 µM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.

Induced mutation in Agaricus bisporus by gamma ray to improve genetic variability, degradation enzyme activity, and yield.

PURPOSE: Genetic variability in white button mushroom cultivars is very low due to the life cycle. Induction mutations using gamma irradiation is a useful way to generate diversity in white button mushrooms to obtain genotype(s) with desirable traits. METHODS: Gamma irradiation Cobalt-60 was used for inducting genetic diversity in white button mushroom to obtain genotype(s) with desirable traits. Gamma irradiation with doses of 0-500 Gy was conducted on spores on Potato Dextrose Agar medium. RESULTS: The results showed significant differences in days to pin production and harvest, fruit body number, fresh and dry weight, yield, laccase, and manganese peroxidase enzyme activity. After isolating variants, 15 variants were selected on the base of their high yield and enzyme degradation activity. Their genetic variation was confirmed by Sequence Related Amplified Polymorphism (SRAP) markers, and then incubated on three types of substrates (50:50, 75:25, and 100:0 % compost: raw straw). The results showed that all variants, except GR18, colonized in 75:25, and GR3, GR4, GR9, GR61, GR72, and GR74 variants colonized in 50:50. In 100:0 substrate, GR55 and GR63 were the earliest variants, and GR9 produced the highest fruit body number. In 75:25 substrate, GR9, GR3, GR61, GR4, GR74, GR4, GR61, and GR72 showed higher yields. The highest laccase and manganese peroxidase activity were recorded in GR3, GR4, GR9, GR72, and GR61. The isolated 15 variants were clustered into two main groups by cluster analysis and genetic variation was confirmed by SRAP markers. CONCLUSION: The results showed that the diversity in the white button mushroom could be improved using gamma rays, and the variation would be useful for the development of future breeding programs.

Inhibitory activity and mechanism of trilobatin on tyrosinase: kinetics, interaction mechanism and molecular docking.

Tyrosinase is the rate-limiting enzyme controlling the production of melanin, and tyrosinase inhibitors can regulate the overproduction of melanin by inhibiting tyrosinase activity, which is an effective method to treat pigmentation disorders. In this study, kinetic analysis, multispectroscopic methods and molecular simulation were used to investigate the inhibitory activity and mechanism of trilobatin on tyrosinase. The kinetic analysis showed that trilobatin had significant inhibitory activity on tyrosinase in a reversible and mixed-type manner with IC50 values of (2.24 ± 0.35) × 10-5 mol L-1. The intrinsic fluorescence of tyrosinase was quenched by trilobatin through a static quenching mechanism. Different spectroscopic measurements demonstrated that trilobatin could change the microenvironments and conformation of tyrosinase and molecular docking determined the binding site of quercetin on tyrosinase.

Preparation and characterization of various chitin-glucan complexes derived from white button mushroom using a deep eutectic solvent-based ecofriendly method.

Deep eutectic solvents (DESs) have gained great interests as ecofriendly and safe solvents in diverse areas. Herein, various chitin-glucan complexes (CGCs) were prepared from white button mushroom (Agaricus bisporus) using DESs. Ultrasonication of mushroom in five DESs yielded two types of CGCs from each DES, one from the DES-insoluble residue (DES_P) and another from the DES-soluble extract (DES_S). The ten resulting CGCs with varying chitin-to-ß-glucan ratios were compared with alkali-insoluble matter (AIM), chemically prepared using NaOH. BU_S and BU_P, prepared using BU comprising betaine and urea, were obtained in the highest yields with reasonably low protein and mineral contents. Despite different acetylation degrees (77.3% and 57.3%, respectively), BU_S and BU_P both degraded at 318 °C and showed remarkably low crystallinity (32.0% and 37.0% for BU_S and BU_P, respectively) compared to AIM, commercial chitin, and the reported CGCs. The surface of BU_S and BU_P was very porous and rough compared with AIM as a result of reduced H-bonds and lowered crystallinity. The DES-based method can potentially enable the preparation of advanced biomaterials from mushrooms under mild and ecofriendly conditions.

Onion juice and extracts for the inhibition of enzymatic browning mechanisms in frozen Agaricus bisporus mushrooms.

BACKGROUND: The potential of onion juice, as well as extracts of waste (tunic) (5%) and fleshy scale leaves (25%), to inhibit enzymatic browning of frozen Agaricus bisporus was investigated. The onion materials were used for blanching and their effectiveness in conserving integrity and appearance of mushroom fruiting bodies was compared with the currently accepted method of blanching in a sodium metabisulfite (SM) solution. RESULTS: It was observed that l-phenylalanine content may be a useful indicator of the changes in enzymatic activity during frozen storage, and l-tyrosine may be an indicator of a loss of lightness in color (parameter L*). The enzymes responsible for color changes were mainly monophenolase (MON) and, to a lesser degree, diphenolase (DIP). After being stored frozen for 8 months, these enzymes were detected at a 29:1 (DIP:MON) ratio in untreated mushrooms and a 2:1 (DIP:MON) ratio in mushrooms treated with onion juice. CONCLUSION: Onion products may be a good alternative to an SM solution. The most effective method to conserve the light color of fruiting bodies was blanching in juice or in an extract of the fleshy scale leaves. The least effective inhibitor of MON was tunic extract, which did, however, cause a favourable increase in the reducing capacity (total polyphenols) and flavonoids. Although the onion waste (tunic) extract changed the color of mushrooms from white to creamy orange, the color of these products was attractive and positively evaluated by panellists. © 2020 Society of Chemical Industry.

Purification and properties of a laccase from the mushroom Agaricus sinodeliciosus.

A homogeneous monomeric laccase (ASL) from Agaricus sinodeliciosus, with a molecular mass of 65 kDa, was isolated using ion-exchange chromatography (CM-cellulose and Q-Sepharose) and gel-filtration chromatography (Superdex 75). This laccase exhibited maximum activity at 50 °C and pH 5.0. Hg2+ and Cd2+ significantly inhibited its activity. The laccase displayed a Km value of 0.9 mM toward 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS). In addition to ABTS, ASL exhibited higher affinity toward o-toluidine and benzidine than other substrates. ASL is able to decolorize malachite green and Eriochrome black T.

Preservation of Agaricus bisporus freshness with using innovative ethylene manipulating active packaging paper.

Agaricus bisporus produces substantial ethylene during storage and transportation, which accelerates ripening and senescence, thereby shortening the shelf-life. In this study, a novel food packaging material with ethylene removal property was prepared to increase storage time of Agaricus bisporus. 1-Methylcyclopropen and molecular sieves loaded with potassium permanganate were used as ethylene scavengers to coat the fresh-keeping paper. SEM, FT-IR and DSC analyses proved that these functional components were successfully coated on the fresh-keeping paper. The qualities of the mushrooms packed by prepared functional paper were then determined. The results showed that this prepared functional paper could delay the softening, browning and weight loss of mushrooms during storage by inhibiting ethylene synthesis-related enzymes and gene expression in the mushroom fruiting body, and continuous adsorption and removal of the exogenous ethylene. Consequently, the functional paper could reduce the biochemical and physicochemical quality loss of Agaricus bisporus, thus prolonging its shelf-life.

Cycling in degradation of organic polymers and uptake of nutrients by a litter-degrading fungus.

Wood and litter degrading fungi are the main decomposers of lignocellulose and thus play a key role in carbon cycling in nature. Here, we provide evidence for a novel lignocellulose degradation strategy employed by the litter degrading fungus Agaricus bisporus (known as the white button mushroom). Fusion of hyphae allows this fungus to synchronize the activity of its mycelium over large distances (50 cm). The synchronized activity has a 13-h interval that increases to 20 h before becoming irregular and it is associated with a 3.5-fold increase in respiration, while compost temperature increases up to 2°C. Transcriptomic analysis of this burst-like phenomenon supports a cyclic degradation of lignin, deconstruction of (hemi-) cellulose and microbial cell wall polymers, and uptake of degradation products during vegetative growth of A. bisporus. Cycling in expression of the ligninolytic system, of enzymes involved in saccharification, and of proteins involved in nutrient uptake is proposed to provide an efficient way for degradation of substrates such as litter.

Plant Nitrilase Homologues in Fungi: Phylogenetic and Functional Analysis with Focus on Nitrilases in Trametes versicolor and Agaricus bisporus.

Fungi contain many plant-nitrilase (NLase) homologues according to database searches. In this study, enzymes NitTv1 from Trametes versicolor and NitAb from Agaricus bisporus were purified and characterized as the representatives of this type of fungal NLase. Both enzymes were slightly more similar to NIT4 type than to NIT1/NIT2/NIT3 type of plant NLases in terms of their amino acid sequences. Expression of the synthetic genes in Escherichia coli Origami B (DE3) was induced with 0.02 mM isopropyl ß-D-1-thiogalactopyranoside at 20 °C. Purification of NitTv1 and NitAb by cobalt affinity chromatography gave ca. 6.6 mg and 9.6 mg of protein per 100 mL of culture medium, respectively. Their activities were determined with 25 mM of nitriles in 50 mM Tris/HCl buffer, pH 8.0, at 30 °C. NitTv1 and NitAb transformed ß-cyano-L-alanine (ß-CA) with the highest specific activities (ca. 132 and 40 U mg-1, respectively) similar to plant NLase NIT4. ß-CA was transformed into Asn and Asp as in NIT4 but at lower Asn:Asp ratios. The fungal NLases also exhibited significant activities for (aryl)aliphatic nitriles such as 3-phenylpropionitrile, cinnamonitrile and fumaronitrile (substrates of NLase NIT1). NitTv1 was more stable than NitAb (at pH 5-9 vs. pH 5-7). These NLases may participate in plant-fungus interactions by detoxifying plant nitriles and/or producing plant hormones. Their homology models elucidated the molecular interactions with various nitriles in their active sites.

4-Fluorobenzylpiperazine-Containing Derivatives as Efficient Inhibitors of Mushroom Tyrosinase.

Tyrosinase is a type-3 copper protein involved in the biosynthesis of melanin pigments; therefore, the inhibition of its enzymatic activity represents a promising strategy for the treatment of hyperpigmentation-related disorders. To address this point, we previously designed a class of 4-(4-fluorobenzyl)piperazin-1-yl-based compounds, which proved to be more active inhibitors against tyrosinase from mushroom Agaricus bisporus than the positive control kojic acid. Herein, we report the synthesis of further series of 4-(4-fluorobenzyl)piperazin-1-yl analogues bearing a (hetero)aromatic fragment as key feature to improve protein affinity. The newly synthesized compounds were assayed in vitro and proved to be potent inhibitors in the low-micromolar range. The active 2-thienyl and 2-furyl derivatives were selected for further modification to allow their binding mode to be analyzed by docking studies and to give satisfactory safety profiles.

Cultivation of Mushrooms and Their Lignocellulolytic Enzyme Production Through the Utilization of Agro-Industrial Waste.

A large amount of agro-industrial waste is produced worldwide in various agricultural sectors and by different food industries. The disposal and burning of this waste have created major global environmental problems. Agro-industrial waste mainly consists of cellulose, hemicellulose and lignin, all of which are collectively defined as lignocellulosic materials. This waste can serve as a suitable substrate in the solid-state fermentation process involving mushrooms. Mushrooms degrade lignocellulosic substrates through lignocellulosic enzyme production and utilize the degraded products to produce their fruiting bodies. Therefore, mushroom cultivation can be considered a prominent biotechnological process for the reduction and valorization of agro-industrial waste. Such waste is generated as a result of the eco-friendly conversion of low-value by-products into new resources that can be used to produce value-added products. Here, we have produced a brief review of the current findings through an overview of recently published literature. This overview has focused on the use of agro-industrial waste as a growth substrate for mushroom cultivation and lignocellulolytic enzyme production.

Structural analysis and allergenicity assessment of an enzymatically cross-linked bovine α-lactalbumin polymer.

Enzymatic cross-linking is frequently used in bio-processing of dairy products since it could change the physiochemical and functional characterization. In our study, bovine α-lactalbumin was cross-linked by polyphenol oxidase from Agaricus bisporus and the changes in the structure, digestibility and allergenicity of α-lactalbumin were explored after cross-linking, and the structural alterations of the polymers were analyzed by circular dichroism spectroscopy, ultraviolet absorption spectroscopy and fluorescence spectroscopy. The digestibility of cross-linked α-lactalbumin was evaluated by simulated digestion in vitro. After that, the allergenicity of α-lactalbumin polymers was evaluated by detection of the specific IgE binding ability using an animal model. The results showed that the secondary and tertiary structures of various α-lactalbumin polymers exhibited a significant variation compared with those of untreated α-lactalbumin, and the cross-linked α-lactalbumin was relatively less susceptible to digestion. Moreover, the allergenicity of cross-linked polymers decreased significantly. These results suggested that there was a direct correlation between a loss of an α-helix and IgE binding to α-lactalbumin, which indicated that enzymatic cross-linking might be an efficient approach to reduce the allergenicity of bovine α-lactalbumin.

Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism.

Tyrosinase is the rate-limiting enzyme for controlling the production of melanin in the human body, and overproduction of melanin can lead to a variety of skin disorders. In this paper, the inhibitory kinetics of phloretin on tyrosinase and their binding mechanism were determined using spectroscopy, molecular docking, antioxidant assays and chromatography. The spectroscopic results indicate that phloretin reversibly inhibits tyrosinase in a mix-type manner through a multiphase kinetic process with the IC50 of 169.36 µmol/L. It is shown that phloretin has a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting that a stable phloretin-tyrosinase complex is generated. Molecular docking results suggest that the dominant conformation of phloretin binds to the gate of the active site of tyrosinase. Moreover, the antioxidant assays demonstrate that phloretin has powerful antioxidant capacity and has the ability to reduce o-dopaquinone to l-dopa just like ascorbic acid. Interestingly, the results of spectroscopy and chromatography indicate that phloretin is a substrate of tyrosinase but also an inhibitor. The possible inhibitory mechanism is proposed, which will be helpful to design and search for tyrosinase inhibitors.

Pyranose dehydrogenases: Rare enzymes for electrochemistry and biocatalysis.

Pyranose dehydrogenase is a flavin-dependent carbohydrate oxidoreductase classified among Auxiliary Activities Family 3, along with structurally and catalytically related enzymes like pyranose oxidase and cellobiose dehydrogenase, and probably fulfils biological functions in lignocellulose breakdown. It is limited to a rather small group of litter-decomposing basidiomycetes adapted to humic-rich habitats, and shows an equally rare combination of structural and biochemical properties. It displays broader substrate specificity and regioselectivity compared to similar enzymes, catalyzing monooxidations at C1, C2, C3 or dioxidations at C2, 3 or C3, 4, depending on the pyranose sugar form (mono-/di-/oligo-saccharide or glycoside) and the enzyme source. It is unable to utilize oxygen as electron acceptor, using substituted benzoquinones and (organo)metallic ions instead, which suggests a role in redox cycling of (hydro)quinones and complexed metal ions. Pyranose dehydrogenase is a promising candidate for enzymatic sensors of various sugars, for the anodic reaction in enzymatic biofuel cells powered by carbohydrate mixtures, and as a versatile biocatalyst for the production of di- and tri-carbonyl sugar derivatives as chiral intermediates for the synthesis of rare sugars, novel drugs and fine chemicals.

Exogenous adenosine triphosphate application retards cap browning in Agaricus bisporus during low temperature storage.

Exogenous adenosine triphosphate (ATP) treatment at 0, 250, 500, 750, and 1000 µM retarded cap browning in mushrooms by 0, 34, 26, 51 and 32 %, respectively, during storage at 4 °C for 18 days. Triggering signaling H2O2 accumulation arising from elevating NADPH oxidase enzyme activity during 6 days of storage at 4 °C may be pivotal for promoting shikimate dehydrogenase enzyme activity in mushrooms treated with ATP during 18 days of storage at 4 °C. Promoting melatonin accumulation (390 µg kg-1 FW vs. 160 µg kg-1 FW) in mushrooms treated with ATP during cold storage may attribute to signaling H2O2 accumulation. Higher DPPH scavenging capacity (72 % vs. 65 %) in mushrooms treated with ATP may attribute to higher phenols accumulation arising from higher phenylalanine ammonialyase/polyphenol oxidase enzymes activity concomitant with higher alternative oxidase gene expression during 18 days of storage at 4 °C.

Evaluation of caffeine as inhibitor against collagenase, elastase and tyrosinase using in silico and in vitro approach.

Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (-4.6 kcal/mol), elastase (-3.36 kcal/mol) and tyrosinase (-2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively.

Phosphonic and Phosphinic Acid Derivatives as Novel Tyrosinase Inhibitors: Kinetic Studies and Molecular Docking.

A dozen of phosphonic and phosphinic acid derivatives containing pyridine moiety were synthesized and its inhibitory activity toward mushroom tyrosinase was investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. All the compounds (1-10) demonstrated the inhibitory effect with the IC50 and inhibition constants ranging millimolar concentrations. The obtained results indicate that the compounds show different types of inhibition (competitive, noncompetitive, mixed), but all of them are reversible inhibitors. The obtained outcomes allowed to make the structure-activity relationship (SAR) analysis. Compound 4 ([(benzylamino)(pyridin-2-yl)methyl]phenylphosphinic acid) revealed the lowest IC50 value of 0.3 mm and inhibitory constant of Ki 0.076 mm, with noncompetitive type and reversible mechanism of inhibition. According to SAR analysis, introducing bulky phenyl moieties to phosphonic and amino groups plays an important role in the inhibitory potency on activity of mushroom tyrosinase and could be useful in design and development of a new class of potent organophosphorus inhibitors of tyrosinase. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties. They may have broad application in food industry and cosmetology.