Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed.

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An Updated Review of Tyrosinase Inhibitors

Biogenic calcium carbonate forms the inorganic component of seashells, otoliths, and many marine skeletons, and its formation is directed by an ordered template of macromolecules. Classical nucleation theory considers crystal formation to occur from a critical nucleus formed by the assembly of ions from solution. Using cryotransmission electron microscopy, we found that template-directed calcium carbonate formation starts with the formation of prenucleation clusters. Their aggregation leads to the nucleation of amorphous nanoparticles in solution. These nanoparticles assemble at the template and, after reaching a critical size, develop dynamic crystalline domains, one of which is selectively stabilized by the template. Our findings have implications for template-directed mineral formation in biological as well as in synthetic systems.

The initial stages of template-controlled CaCO3 formation revealed by Cryo-TEM

Lead Authors: Marco Bindi (Italy), Sally Brown (UK), Ines Camilloni (Argentina), Arona Diedhiou (Ivory Coast/Senegal), Riyanti Djalante (Japan/Indonesia), Kristie L. Ebi (USA), Francois Engelbrecht (South Africa), Joel Guiot (France), Yasuaki Hijioka (Japan), Shagun Mehrotra (USA/India), Antony Payne (UK), Sonia I. Seneviratne (Switzerland), Adelle Thomas (Bahamas), Rachel Warren (UK), Guangsheng Zhou (China)

Impacts of 1.5°C Global Warming on Natural and Human Systems

Tyrosinase catalyzes the conversion of phenolic compounds into their quinone derivatives, which are precursors for the formation of melanin, a ubiquitous pigment in living organisms. Because of its importance for browning reactions in the food industry, the tyrosinase from the mushroom Agaricus bisporus has been investigated in depth. In previous studies the tyrosinase enzyme complex was shown to be a H(2)L(2) tetramer, but no clues were obtained of the identities of the subunits, their mode of association, and the 3D structure of the complex. Here we unravel this tetramer at the molecular level. Its 2.3 A resolution crystal structure is the first structure of the full fungal tyrosinase complex. The complex comprises two H subunits of ∼392 residues and two L subunits of ∼150 residues. The H subunit originates from the ppo3 gene and has a fold similar to other tyrosinases, but it is ∼100 residues larger. The L subunit appeared to be the product of orf239342 and has a lectin-like fold. The H subunit contains a binuclear copper-binding site in the deoxy-state, in which three histidine residues coordinate each copper ion. The side chains of these histidines have their orientation fixed by hydrogen bonds or, in the case of His85, by a thioether bridge with the side chain of Cys83. The specific tyrosinase inhibitor tropolone forms a pre-Michaelis complex with the enzyme. It binds near the binuclear copper site without directly coordinating the copper ions. The function of the ORF239342 subunits is not known. Carbohydrate binding sites identified in other lectins are not conserved in ORF239342, and the subunits are over 25 A away from the active site, making a role in activity unlikely. The structures explain how calcium ions stabilize the tetrameric state of the enzyme.

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Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone.

Metabolites from symbiotic bacteria

Mushroom tyrosinase (EC 1.14.18.1) is a copper containing oxidase that catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones, and then forms brown or black pigments. In the present study, the effects of some flavonoids on the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) have been studied. The results show that flavonoids can lead to reversible inhibition of the enzyme. A kinetic analysis showed that the flavonols are competitive inhibitors, whereas luteolin is an uncompetitive inhibitor. The rank order of inhibition was: quercetin > galangin > morin; fisetin > 3,7,4"-trihydroxyflavone; luteolin > apigenin > chrysin.

Inhibitory Effects of Some Flavonoids on the Activity of Mushroom Tyrosinase

Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production.

Understanding the molecular composition is of great interest for both nacre formation mechanism and biomineralization in mollusk shell. A cDNA clone encoding an MSI31 relative, termed MSI7 because of its estimated molecular mass of 7.3 kDa, was isolated from the pearl oyster, Pinctada fucata . This novel protein shares similarity with MSI31, a prismatic framework protein of P. fucata . It is peculiar that MSI7 is much shorter in size, harboring only the Gly-rich sequence that has been proposed to be critical for Ca 2+ binding. In situ hybridization result showed that MSI7 mRNA was expressed specifically at the folds and outer epithelia of the mantle, indicating that MSI7 participates in the framework formation of both the nacreous layer and prismatic layer. In vitro experiment on the function of MSI7 suggested that it accelerates the nucleation and precipitation of CaCO 3 . Taken together, we have identified a novel matrix protein of the pearl oyster, which may play an important role in determining the texture of nacre.

A novel matrix protein participating in the nacre framework formation of pearl oyster, Pinctada fucata

A novel matrix protein family participating in the prismatic layer framework formation of pearl oyster, Pinctada fucata.

Bee venom has been reported to exhibit antitumour activity in-vitro and in-vivo. Apoptosis, necrosis and lysis of tumour cells were suggested as possible mechanisms by which bee venom inhibited tumour growth. The aim of this study was to investigate potential mechanisms by which bee venom inhibits K1735M2 mouse melanoma cells in-vitro and B16 melanoma, a transplantable solid melanoma in C57BL/6 mice, in-vivo. The proliferation of K1735M2 cells in-vitro was inhibited by bee venom in a concentration- and time-dependent manner. The inhibition was indicated by the arrest of the cell cycle at the G1 stage, as detected by flow cytometric measurements. The bee venom induced apoptosis-like cell death as identified by histological observations and by DNA fragmentation. In the in-vivo experiments, the bee venom (1.0, 3.0, 9.0 mg kg-1 of body weight, on days 1-12) was injected intraperitoneally into mice 24 h after the mice were inoculated with B16 cells. Inhibition of the solid tumour was observed. Apoptosis of the K1735M2 cells was suggested as the possible mechanism by which bee venom inhibited cell proliferation and induced K1735M2 cell differentiation in-vitro. The in-vivo experiment indicated that bee venom could be used as a chemotherapeutic agent against malignant tumours.

Liping Xie

Papers

Inhibitory Effects of Some Flavonoids on the Activity of Mushroom Tyrosinase

Daidzein enhances osteoblast growth that may be mediated by increased bone morphogenetic protein (BMP) production.

A novel matrix protein participating in the nacre framework formation of pearl oyster, Pinctada fucata

A novel matrix protein family participating in the prismatic layer framework formation of pearl oyster, Pinctada fucata.

Effect of honey bee venom on proliferation of K1735M2 mouse melanoma cells in-vitro and growth of murine B16 melanomas in-vivo.