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Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications

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Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications biosensors Review Spectrophotometric Assays for Sensing Tyrosinase Activity and Their Applications Yu-Fan Fan 1,†, Si-Xing Zhu 2,†, Fan-Bin Hou 1, Dong-Fang Zhao 1, Qiu-Sha Pan 1, Yan-Wei Xiang 3, Xing-Kai Qian 1, Guang-Bo Ge 1 and Ping Wang 1,* 1 Shanghai Frontiers Science Center for Chinese Medicine Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shangha 201203, China; [email protected] (Y.-F.F.); [email protected] (F.-B.H.); [email protected] (D.-F.Z.); [email protected] (Q.-S.P.); [email protected] (X.-K.Q.); [email protected] (G.-B.G.) 2 Institute of Science, Technology and Humanities, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; [email protected] 3 School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Tyrosinase (TYR, E.C. 1.14.18.1), a critical enzyme participating in melanogenesis, catalyzes the first two steps in melanin biosynthesis including the ortho-hydroxylation of L-tyrosine and the oxidation of L-DOPA. Previous pharmacological investigations have revealed that an abnormal level of TYR is tightly associated with various dermatoses, including albinism, age spots, and malignant melanoma. TYR inhibitors can partially block the formation of pigment, which are always used for improving skin tone and treating dermatoses. The practical and reliable assays for monitoring TYR activity levels are very useful for both disease diagnosis and drug discovery. This review comprehensively summarizes structural and enzymatic characteristics, catalytic mechanism and Citation: Fan, Y.-F.; Zhu, S.-X.; Hou, substrate preference of TYR, as well as the recent advances in biochemical assays for sensing TYR F.-B.; Zhao, D.-F.; Pan, Q.-S.; Xiang, activity and their biomedical applications. The design strategies of various TYR substrates, alongside Y.-W.; Qian, X.-K.; Ge, G.-B.; Wang, P. with several lists of all reported biochemical assays for sensing TYR including analytical conditions Spectrophotometric Assays for Sensing and kinetic parameters, are presented for the first time. Additionally, the biomedical applications Tyrosinase Activity and Their and future perspectives of these optical assays are also highlighted. The information and knowledge Applications. Biosensors 2021, 11, 290. presented in this review offer a group of practical and reliable assays and imaging tools for sensing https://doi.org/10.3390/bios11080290 TYR activities in complex biological systems, which strongly facilitates high-throughput screening TYR inhibitors and further investigations on the relevance of TYR to human diseases. Received: 9 July 2021 Accepted: 19 August 2021 Keywords: tyrosinase (TYR); enzymatic activity; optical substrates; TYR inhibitors; high-throughput Published: 23 August 2021 screening Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- 1. Introduction iations. Tyrosinase (TYR, E.C. 1.14.18.1), a type-3 binuclear copper-containing oxidoreductase, efficiently catalyzes o-hydroxylation of monophenols to diphenols (monophenolase activity) and the oxidation of diphenols to quinones (diphenolase activity), without any additional cofactors (Figure1)[ 1,2]. It is ubiquitously distributed in organisms ranging from bacteria Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. to eukaryotes and plays a pivotal role in the enzymatic browning of fruit or fungi, as well This article is an open access article as mammalian melanin synthesis [3,4]. In mammals, melanin is exclusively synthesized in distributed under the terms and melanosomes via complex biochemical reactions (Figure2), and this endogenous substance conditions of the Creative Commons is primarily responsible for the pigmentation of retina and skin [5,6]. TYR catalyzes the Attribution (CC BY) license (https:// first two steps in melanin biosynthesis: the o-hydroxylation of L-tyrosine and the oxidation creativecommons.org/licenses/by/ of L-DOPA. Since the remainder of the reaction sequence can proceed spontaneously at 4.0/). physiological pH, the conversion of L-tyrosine to dopaquinone (DQ) has been implicated as Biosensors 2021, 11, 290. https://doi.org/10.3390/bios11080290 https://www.mdpi.com/journal/biosensors Biosensors 2021, 11, x FOR PEER REVIEW 2 of 22 Biosensors 2021, 11 , x FOR PEER REVIEW 2 of 22 Biosensors 2021 11 L-tyrosine and the oxidation of L-DOPA. Since the remainder of the reaction sequence , , 290L-tyrosine and the oxidation of L-DOPA. Since the remainder of the reaction sequence 2 of 22 can proceed spontaneously at physiological pH, the conversion of L-tyrosine to do- can proceed spontaneously at physiological pH, the conversion of L-tyrosine to do- paquinone (DQ) has been implicated as a crucial rate-limiting procedure in melanogene- paquinone (DQ) has been implicated as a crucial rate-limiting procedure in melanogene- sis [7,8]. DQ could spontaneously convert into dopachrome, which gradually decom- sis [7,8]. DQ acould crucial spontaneously rate-limiting procedureconvert into in melanogenesisdopachrome, which [7,8]. DQ gradually could spontaneously decom- convert poses into 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid poses into 5,6-dihydroxyindoleinto dopachrome, which (DHI) gradually and decomposes5,6-dihydroxyindole-2-carboxylic into 5,6-dihydroxyindole acid (DHI) and 5,6- (DHICA) through a succession of redox reactions [5,9]. Ultimately, these dihydroxyin- (DHICA) throughdihydroxyindole-2-carboxylic a succession of redox reacti acidons (DHICA) [5,9]. Ultimately, through a succession these dihydroxyin- of redox reactions [5,9]. doles are oxidized to eumelanin. Alongside, in the presence of cysteine or glutathione, doles are oxidizedUltimately, to eumelanin. these dihydroxyindoles Alongside, in the are oxidizedpresence toof eumelanin.cysteine or Alongside,glutathione, in the presence DQ is converted to 5-S-cysteinyl dopa or glutothionyl dopa, finally yielding pheomelanin DQ is convertedof cysteineto 5-S-cysteinyl or glutathione, dopa or glutothionyl DQ is converted dopa, to finally 5-S-cysteinyl yielding dopa pheomelanin or glutothionyl dopa, [10,11]. The types and relative amounts of these melanin constitute color-based ethnic [10,11]. The typesfinally and yielding relative pheomelanin amounts of [these10,11 ].melanin The types constitute and relative color-based amounts ethnic of these melanin diversification. Three tyrosinase-like enzymes co-regulate melanogenesis, including TYR diversification.constitute Three tyrosinase-like color-based ethnicenzymes diversification. co-regulate melanogenesis, Three tyrosinase-like including enzymes TYR co-regulate and TYR-related proteins 1 (TRP-1) and 2 (TRP-2). TRP-1 shows DHICA oxidase and low and TYR-relatedmelanogenesis, proteins 1 (TRP-1) including and TYR2 (TRP-2). and TYR-related TRP-1 shows proteins DHICA 1 oxidase (TRP-1) and and low 2 (TRP-2). TRP-1 tyrosine hydroxylase activity when zinc is replaced by copper. TRP-2 contains two zinc tyrosine hydroxylaseshows DHICA activity oxidase when zinc and lowis replaced tyrosine by hydroxylase copper. TRP-2 activity contains when zinctwo iszinc replaced by cop- ions at the active site and isomerizes dopachrome to DHICA. They are metal-containing ions at the activeper. site TRP-2 and contains isomerizes two dopa zinc ionschrome at the to activeDHICA. site They and isomerizesare metal-containing dopachrome to DHICA. glycoproteins and share ~40% amino acid sequence identity and ~70% similarity [1]. glycoproteinsThey and areshare metal-containing ~40% amino acid glycoproteins sequence and identity share ~40%and ~70% amino similarity acid sequence [1]. identity and Despite TYR and TYR-related proteins 1 (TRP-1) and 2 (TRP-2) being necessary for mel- Despite TYR ~70%and TYR-related similarity [ 1proteins]. Despite 1 (TRP-1) TYR and and TYR-related 2 (TRP-2) proteinsbeing necessary 1 (TRP-1) for and mel- 2 (TRP-2) being anogenesis, TYR is the most critical rate-limiting enzyme [10]. anogenesis, TYRnecessary is the most for melanogenesis, critical rate-limiting TYR is enzyme the most [10]. critical rate-limiting enzyme [10]. Figure 1. The slow ortho-hydroxylation of monophenol and the fast oxidation of catechol catalyzed FigureFigure 1. The 1. slow The orthoslow-hydroxylation ortho-hydroxylation of monophenol of monophenol and the and fast the oxidation fast oxidation of catechol of catechol catalyzed catalyzed by TYR. by TYR. by TYR. Figure 2. Biosynthetic pathway of melanin [7,8,10]. DQ: dopaquinone; L-Dopa: Figure 2. BiosyntheticFigure 2. Biosyntheticpathway of pathway melanin of melanin[7,8,10]. [7DQ:,8,10 ].dopaquinone; DQ: dopaquinone; L-Dopa: L-Dopa: L-3,4- L-3,4-dihydroxyphenylalanine; DHICA: 5,6-dihydroxyindole-2 carboxylic acid; DHI: L-3,4-dihydroxyphenylalanine;dihydroxyphenylalanine; DHICA: DHICA: 5,6- 5,6-dihydroxyindole-2dihydroxyindole-2 carboxylic acid;acid; DHI: 5,6-dihydroxyindole;DHI: 5,6-dihydroxyindole; ICAQ: indole-2-carboxylic acid-5,6-quinone; IQ: indole-5,6-quinone; HBTA: 5,6-dihydroxyindole;ICAQ: ICAQ: indole-2-carboxylic indole-2-carboxylic acid-5,6-quinone; acid-5,6-quinone; IQ: IQ: indole-5,6-quinone; indole-5,6-quinone; HBTA: HBTA: 5-hydroxy-1,4- 5-hydroxy-1,4-benzothiazinylalanine. 5-hydroxy-1,4-benzothiazinylalanine.benzothiazinylalanine. Recent pharmacological
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