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The melanin produced by Aureobasidium melanogenum XJ5-1 obtained from the Taklimakan Desert can play an important role in adaptation of the yeast strain to various stress treatments. It is very important to know how the desert-derived yeast sense, respond and adapt to the harsh environments. However, it is still unclear how melanin is genetically controlled by signaling pathways and transcriptional factors. In this study, it was found that the mitogen-activated protein kinase (MAPK) Slt2 in the cell wall integrity (CWI) signal pathway could regulate activity of the transcriptional activator Swi4; in turn, the Swi4 could control the expression of the CMR1 gene. The melanin-specific transcriptional activator Cmr1 encoded by the CMR1 gene was specifically bound to the promoter with the sequence TTCTCTCCA of the PKS1 gene and strongly stimulated expression of the PKS1 gene and any other genes responsible for melanin biosynthesis, so that a large amount of melanin could be produced by A. melanogenum XJ5-1. Therefore, melanin biosynthesis in the desert-derived A. melanogenum XJ5-1 was controlled mainly by the CWI signal pathway among the cell wall-related signal pathways via a transcriptional activator Cmr and regulation of the melanin biosynthesis in A. melanogenum XJ5-1 was completely different from that of the melanin biosynthesis in any other fungi. This is the first time to show that melanin biosynthesis in the desert-derived A. melanogenum XJ5-1 is controlled mainly by the CWI signal pathway via a transcriptional activator Cmr1. This would provide the fundamentals for further research on the desert-derived yeast to sense, respond and adapt to the harsh environments.

The chemical modification and optimization of biologically active compounds are essential steps in the identification of promising lead compounds for drug development. We previously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives of chalcone 21 and evaluated their anti-melanogenic activity in α-MSH-induced B16F10 cells. (E)-N-(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21) exhibited the strongest inhibition of cellular melanin production, with an IC50 value of 0.54 μM. It was more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin, whose IC50 values were 4.9, 38.5, and 148.4 μM, respectively. Chalcone 21-21 decreased the expression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF, the phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our results demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic activity.

The filamentous ascomycete Sordaria macrospora accumulates melanin during sexual development. The four melanin biosynthesis genes pks, teh, sdh and tih were isolated and their homology to genes involved in 1,8 dihydroxynaphthalene (DHN) melanin biosynthesis was shown. The presence of DHN melanin in S. macrospora was further confirmed by disrupting the pks gene encoding a putative polyketide synthase and by RNA interference-mediated silencing of the sdh gene encoding a putative scytalone dehydratase. Because melanin occurs in fruiting bodies that develop through several intermediate stages within 7 days of growth, a Northern analysis of a developmental time-course was conducted. These data revealed a time-dependent regulation of teh and sdh transcript levels. Comparing the transcriptional expression by real-time PCR of melanin biosynthesis genes in the wild type under conditions allowing or repressing sexual development, a significant downregulation during vegetative growth was detected. Quantitative real-time PCR and Northern blot analysis of melanin biosynthesis gene expression in different developmental mutants confirmed that melanin biosynthesis is linked to fruiting body development and is under the control of specific regulatory genes that participate in sexual differentiation.

Background The annual fish Nothobranchius furzeri is characterized by a natural dichromatism with yellow-tailed and red-tailed male individuals. These differences are due to different distributions of xanthophores and erythrophores in the two morphs. Previous crossing studies have showed that dichromatism in N. furzeri is inherited as a simple Mendelian trait with the yellow morph dominant over the red morph. The causative genetic variation was mapped by linkage analysis in a chromosome region containing the Mc1r locus. However, subsequent mapping showed that Mc1r is most likely not responsible for the color difference in N. furzeri . To gain further insight into the molecular basis of this phenotype, we performed RNA-seq on F2 progeny of a cross between N. furzeri male and N. kadleci female. Results We identified 210 differentially-expressed genes between yellow and red fin samples. Functional annotation analysis revealed that genes with higher transcript levels in the yellow morph are enriched for the melanin synthesis pathway indicating that xanthophores are more similar to melanophores than are the erythrophores. Genes with higher expression levels in red-tails included xanthine dehydrogenase ( Xdh ), coding for a biosynthetic enzyme in the pteridine synthesis pathway, and genes related to muscle contraction. Comparison of DEGs obtained in this study with genes associated with pigmentation in the Midas cichlid ( A. citrinellus ) reveal similarities like involvement of the melanin biosynthesis pathway, the genes Ptgir , Rasef (RAS and EF-hand domain containing), as well as genes primarily expressed in muscle such as Ttn and Ttnb (titin, titin b). Conclusions Regulation of genes in the melanin synthetic pathway is an expected finding and shows that N. furzeri is a genetically-tractable species for studying the genetic basis of natural phenotypic variations. The current list of differentially-expressed genes can be compared with the results of fine-mapping, to reveal the genetic architecture of this natural phenotype. However, an evolutionarily-conserved role of muscle-related genes in tail fin pigmentation is novel finding and interesting perspective for the future.

Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms.

Melanogenesis is a process to synthesize melanin, which is a primary responsible for the pigmentation of human skin, eye and hair. Although numerous enzymatic catalyzed and chemical reactions are involved in melanogenesis process, the enzymes such as tyrosinase and tyrosinase-related protein-1 (TRP-1) and TRP-2 played a major role in melanin synthesis. Specifically, tyrosinase is a key enzyme, which catalyzes a rate-limiting step of the melanin synthesis, and the downregulation of tyrosinase is the most prominent approach for the development of melanogenesis inhibitors. Therefore, numerous inhibitors that target tyrosinase have been developed in recent years. The review focuses on the recent discovery of tyrosinase inhibitors that are directly involved in the inhibition of tyrosinase catalytic activity and functionality from all sources, including laboratory synthetic methods, natural products, virtual screening and structure-based molecular docking studies.

Melanin is a unique pigment with myriad functions that is found in all biological kingdoms. It is multifunctional, providing defense against environmental stresses such as ultraviolet (UV) light, oxidizing agents and ionizing radiation. Melanin contributes to the ability of fungi to survive in harsh environments. In addition, it plays a role in fungal pathogenesis. Melanin is an amorphous polymer that is produced by one of two synthetic pathways. Fungi may synthesize melanin from endogenous substrate via a 1,8-dihydroxynaphthalene (DHN) intermediate. Alternatively, some fungi produce melanin from l-3,4-dihydroxyphenylalanine (l-dopa). The detailed chemical structure of melanin is not known. However, microscopic studies show that it has an overall granular structure. In fungi, melanin granules are localized to the cell wall where they are likely cross-linked to polysaccharides. Recent studies suggest the fungal melanin may be synthesized in internal vesicles akin to mammalian melanosomes and transported to the cell wall. Potential applications of melanin take advantage of melanin's radioprotective properties and propensity to bind to a variety of substances. [PUBLICATION ABSTRACT]

Skin color varies among human populations and is thought to be under selection, with light skin maximizing vitamin D production at higher latitudes and dark skin providing UV protection in equatorial zones. To identify the genes that give rise to the palette of human skin tones, Crawford et al. applied genome-wide analyses across diverse African populations (see the Perspective by Tang and Barsh). Genetic variants were identified with likely function in skin phenotypes. Comparison to model organisms verified a conserved function of MFSD12 in pigmentation. A global genetic panel was used to trace how alleles associated with skin color likely moved across the globe as humans migrated, both within and out of Africa. Science , this issue p. eaan8433 ; see also p. 867 Genome-wide analysis of 2000 Africans identifies and functionally characterizes pigmentation loci. Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5 , MFSD12 , DDB1 , TMEM138 , OCA2 , and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in South Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of ultraviolet response genes under selection in Eurasians.

In Parkinson’s disease (PD) there is a selective degeneration of neuromelanin-containing neurons, especially substantia nigra dopaminergic neurons. In humans, neuromelanin accumulates with age, the latter being the main risk factor for PD. The contribution of neuromelanin to PD pathogenesis remains unknown because, unlike humans, common laboratory animals lack neuromelanin. Synthesis of peripheral melanins is mediated by tyrosinase, an enzyme also present at low levels in the brain. Here we report that overexpression of human tyrosinase in rat substantia nigra results in age-dependent production of human-like neuromelanin within nigral dopaminergic neurons, up to levels reached in elderly humans. In these animals, intracellular neuromelanin accumulation above a specific threshold is associated to an age-dependent PD phenotype, including hypokinesia, Lewy body-like formation and nigrostriatal neurodegeneration. Enhancing lysosomal proteostasis reduces intracellular neuromelanin and prevents neurodegeneration in tyrosinase-overexpressing animals. Our results suggest that intracellular neuromelanin levels may set the threshold for the initiation of PD. It is unclear if neuromelanin plays a role in Parkinson’s disease pathogenesis since common laboratory animals lack this pigment. Authors show here that overexpression of human tyrosinase in the substantia nigra of rats resulted in an age-dependent production of human-like neuromelanin within nigral dopaminergic neurons and is associated with a Parkinson’s disease phenotype when allowed to accumulate above a specific threshold.

In this present study, a newly isolated strain, Streptomyces sp. NEAE-H, capable of producing high amount of black extracellular melanin pigment on peptone-yeast extract iron agar and identified as Streptomyces glaucescens NEAE-H. Plackett–Burman statistical design was conducted for initial screening of 17 independent (assigned) variables for their significances on melanin pigment production by Streptomyces glaucescens NEAE-H. The most significant factors affecting melanin production are incubation period, protease-peptone and ferric ammonium citrate. The levels of these significant variables and their interaction effects were optimized by using face-centered central composite design. The maximum melanin production (31.650 μg/0.1 ml) and tyrosinase activity (6089.10 U/ml) were achieved in the central point runs under the conditions of incubation period (6 days), protease-peptone (5 g/L) and ferric ammonium citrate (0.5 g/L). Melanin pigment was recovered by acid-treatment. Higher absorption of the purified melanin pigment was observed in the UV region at 250 nm. It appeared to have defined small spheres by scanning electron microscopy imaging. The maximum melanin yield was 350 mg dry wt/L of production medium. In vitro anticancer activity of melanin pigment was assayed against skin cancer cell line using MTT assay. The IC 50 value was 16.34 ± 1.31 μg/ml for melanin and 8.8 ± 0.5 μg/ml for standard 5-fluorouracil.