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.

/pdf/crystal-structure-of-agaricus-bisporus-mushroom-tyrosinase-5egq24ti7m.pdf

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

Tyrosinase plays a pivotal role in the synthesis of melanin pigment synthesis on skin utilizing tyrosine as a substrate. Melanin is responsible for the protection against harmful ultraviolet irradiation, which can cause significant pathological conditions, such as skin cancers. However, it can also create esthetic problems when accumulated as hyperpigmented spots. Various skin-whitening ingredients which inhibit tyrosinase activity have been identified. Some of them, especially ones with natural product origins, possess phenolic moiety and have been employed in cosmetic products. Semi-synthetic and synthetic inhibitors have also been developed under inspiration of the natural inhibitors yet some of which have no phenolic groups. In this review, tyrosinase inhibitors with natural, semi-synthetic and synthetic origins are listed up with their structures, activities and characteristics. Further, a recent report on the adverse effect of a natural melanin synthesis inhibitor which was included in skin-whitening cosmetics is also briefly discussed.

https://www.tandfonline.com/doi/pdf/10.3109/14756366.2015.1004058

Natural, semisynthetic and synthetic tyrosinase inhibitors

Melanogenesis is a biosynthetic pathway for the formation of the pigment melanin in human skin. A key enzyme, tyrosinase, catalyzes the first and only rate-limiting steps in melanogenesis, and the down-regulation of enzyme activity is the most reported method for the inhibition of melanogenesis. Because of the cosmetically important issue of hyperpigmentation, there is a big demand for melanogenesis inhibitors. This encourages researchers to seek potent melanogenesis inhibitors for cosmetic uses. This article reviews melanogenesis inhibitors that have been recently discovered from natural sources. The reaction mechanisms of the inhibitors on tyrosinase activity are also discussed.

Natural Melanogenesis Inhibitors Acting Through the Down-Regulation of Tyrosinase Activity

Natural ingredients have been used for centuries for skin care purposes. Nowadays, they are becoming more prevalent in formulations, due to consumers’ concerns about synthetic ingredients/chemical substances. The main benefits reported for plant extracts, used in skin care, include antioxidant and antimicrobial activities and tyrosinase inhibition effect. In this review, some examples of plants from Portuguese flora, whose extracts have shown good properties for skin care are presented. However, despite the known properties of plant extracts, few studies reported the development of formulations with them. More work in this field can be accomplished to meet consumer demand.

/pdf/main-benefits-and-applicability-of-plant-extracts-in-skin-5197q08jxb.pdf

Main Benefits and Applicability of Plant Extracts in Skin Care Products

Phytochemistry and biological properties of glabridin.

Skin-lightening products are commercially available for cosmetic purposes to obtain lighter skin complexion. Clinically, they are also used for treatment of hyperpigmentary disorders such as melasma, cafe au lait spot and solar lentigo. All of these target naturally melanin production, and many of the commonly used agents are known as competitive inhibitors of tyrosinase, one of the key enzymes in melanogenesis. In this review, we present an overview of commonly used skin-whitening ingredients that are commercialized, but we also hypothesize on other mechanisms that could be important targets to control skin pigmentation such as for example regulation of the adrenergic and glutaminergic signalling and also control of tetrahydrobiopterins in the human skin.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1468-2494.2010.00616.x

The melanogenesis and mechanisms of skin-lightening agents--existing and new approaches

There are trillions of live bacteria, of around 1000 different species, living in human skin which are considered essential for the balance and barrier function of the skin. The gut microbiome has been a subject of extensive research and evidence shows that the gut flora is affected by preservatives and processed foods. In conventional skincare, preservatives are used, and this raises the question of how it affects the skin flora and its balance.

Randomized comparative double‐blind study assessing the difference between topically applied microbiome supporting skincare versus conventional skincare on the facial microbiome in correlation to biophysical skin parameters

Johanna M. Gillbro

Papers

The melanogenesis and mechanisms of skin-lightening agents--existing and new approaches

Randomized comparative double‐blind study assessing the difference between topically applied microbiome supporting skincare versus conventional skincare on the facial microbiome in correlation to biophysical skin parameters