Pigments produced by different microorganisms. Adapted from Ref. [3].
Abstract
Production of the microbial pigments is one of the emerging fields of research due to a growing interest of the industry for safer products, easily degradable and eco-friendly. Fungi constitute a valuable source of pigments because they are capable of producing high yields of the substance in the cheap culture medium, making the bioprocess economically viable on the industrial scale. Some fungal species produce a dark-brown pigment, known as melanin, by oxidative polymerization of phenolic compounds, such as glutaminyl-3,4-dihydroxybenzene (GDHB) or catechol or 1,8-dihydroxynaphthalene (DHN) or 3,4-dihydroxyphenylalanine (DOPA). This pigment has been reported to act as “fungal armor” due to its ability to protect fungi from adverse conditions, neutralizing oxidants generated in response to stress. Apart from the scavenging activity, melanin exhibits other biological activities, including thermoregulatory, radio- and photoprotective, antimicrobial, antiviral, cytotoxic, anti-inflammatory, and immunomodulatory. Studies have shown that the media composition and cultivation conditions affect the pigment production in fungi and the manipulation of these parameters can result in an increase in pigment yield for large-scale pigment production. This chapter presents a comprehensive discussion of the research on fungal melanin, including the recently discovered biological activities and the potential use of this pigment for various biotechnological applications in the fields of biomedicine, dermocosmetics, materials science, and nanotechnology.
Keywords
- fungi
- pigment
- melanin
- biological activity
- industrial applications
1. Introduction
Considering the harmful effects of synthetic dyes on human health and to the environment, developmental process for obtaining pigments from natural sources has become significant worldwide. Microbial pigments have gained attention owing to a growing interest of the industry in safer products, easily degradable, eco-friendly and do not cause harmful effects. The pigment production from microorganisms is considered more advantageous because it is a more efficient and cost-effective process than chemical synthesis of pigments. Microorganisms are also more feasible sources of pigments in comparison to pigments extracted from plants and animals because they do not have seasonal constraints, do not compete for limited farming land with actual foods, and can be produced easily in the cheap culture medium with high yields [1–6]. Besides, the microorganisms produce an extraordinary range of pigments that include several chemical classes such as carotenoids, melanins, flavins, phenazines, quinones, monascins, violacein, or indigo, as shown in Table 1.
Pigment | Microorganism |
---|---|
Indigoidine (blue-green) | |
Carotenoid (orange) | |
Melanin (black-brown) | |
Prodigiosin (red) | |
Zeaxanthin (yellow) | |
Canthaxanthin (orange) | |
Xanthomonadin (yellow) | |
Astaxanthin (red) | |
Violacein (purple) | |
Anthraquinone (red) | |
Halorhodopsin and rhodopsin (pink | |
Rosy pink | |
Violet/purple | |
Rosy peach | |
Orange brown | |
Pink/purple violet |
Among microbial species, fungi represent an economically significant source of these compounds because they can act as microbial cell factories producing high yields of metabolites with great diverse chemical structures combined with ease of large-scale cultivation [7–9].
As shown in Table 1, some fungal species produce a dark-brown pigment, known as melanin. In general, this pigment is located in the outermost layer of the cell wall associated with chitin (referred as cell wall-bound melanin), but in some fungi, melanin can also be found outside the fungal cell, usually in the form of granules in culture fluids [10].
Fungal melanins are negatively charged, hydrophobic pigments of high molecular weight formed by oxidative polymerization from phenolic and/or indolic compounds, such as glutaminyl-3,4-dihydroxybenzene (GDHB) or catechol or 1,8-dihydroxynaphthalene (DHN) or 3,4-dihydroxyphenylalanine (DOPA). Most Ascomycota fungi synthesize DHN-melanin from the polyketide synthase pathway, whereas few species are able to produce melanin through L-DOPA, in a pathway that resembles mammalian melanin biosynthesis [11–13].
The melanin pigment is not essential for fungal development, but it has been reported to act as “fungal armor” due to its ability to protect the microorganisms from harmful environmental conditions. In vitro studies have shown that melanized fungi are more resistant to UV light-induced and oxidant-mediated damages, temperature extremes, hydrolytic enzymes, heavy metal toxicity, and antimicrobial drugs than those nonmelanized [10, 14–17]. Recent studies have shown that in industrial and roadside areas, there is an increase in the proportion of dark melanin-containing fungi, as
The presence of melanin in the cell wall is also correlated with enhanced virulence of parasitic fungi, as
Although the molecular structure of fungal melanin remains enigmatic, significant progress has been made in understanding particular aspects of its macro- and microstructure. These advances allow to elucidate the molecular mechanisms of the various biological functions of melanin [22]. Studies have shown that the effect of melanin enhancing the survival of fungi under adverse conditions can be mainly due to its powerful free radical scavenger properties, acting as a “sponge” for other free radicals generated by the fungus in response to environmental stress [20, 29, 30]. Apart from this scavenging ability, melanin exhibits other biological activities, including thermoregulatory, photoprotective, antimicrobial, antiviral, cytotoxic, anti-inflammatory, radioprotective, and immunomodulatory [13, 17, 18, 31–34].
Since melanin has characteristics of functional materials and bioorganic, a growing number of researchers see this pigment with great interest, taking advantage of their properties for numerous biotechnological applications in cosmetics, pharmaceutical, electronic, and food processing industries [12, 19, 35].
The purpose of this chapter involves a comprehensive discussion of the research on fungal melanin, including the recently discovered biological activities and the potential use of this pigment for several biotechnological applications. Additionally, we discussed the ways to explore the metabolic potential of the pigment-producing fungi by manipulation of cultivation conditions to improve performance of the process, increasing yields, and reducing cost, for large-scale production.
2. Factors influencing the melanin production
Microbial pigment production is now one of the emerging fields of research due to its potential for various industrial applications, as foodstuff, cosmetics, pharmaceutical, and textile manufacturing processes. However, it is known that for the success of microbial fermentation processes, it is necessary to choose the correct productive culture strain and to determine the appropriate cultivation conditions [4, 8, 36].
An ideal pigment-producing microorganism should be capable of using a wide range of C and N sources; must be tolerant to pH, temperature, and minerals concentration; and must give reasonable pigments yield. The nontoxic and nonpathogenic natures, coupled with easy separation from cell biomass, are also preferred qualities. The potential of using filamentous fungi as pigment sources is due to their extraordinary metabolic versatility because they can be cultivated over a wide range of temperatures (10–50°C), pH (2–11), salinity (0–34%), and water activity (0.6–1) and under oligotrophic or nutrient-rich conditions. They can grow in different culture systems (submerged and solid), and fermentation protocols have been established for large-scale industrial processes. In addition, these organisms can be genetically modified to increase productivity and quality of the produced pigments [37, 38].
In order to improve performance and reduce the cost of pigments produced by microbial fermentation, it is essential to identify the nutritional and physical factors that have a greater influence on the cell growth and metabolite biosynthesis [4, 6, 39, 40].
Several studies have shown that the composition of the growth medium, nature and concentration of carbon and nitrogen sources, minerals, vitamins, temperature, pH, the presence of oxygen and aeration, light, stress, and irradiation, among others, affect the growth and pigment production in fungi and that the manipulation of the culture conditions can result in enhanced pigment production [41–47].
Experimental evidences indicate that the growth temperature influences the performance of the pigment production process, but this effect depends on the type of organism.
Researches support that the pH of the medium also affects the growth of fungi and type of pigment produced. In species of
The influence of light on intra- and extracellular pigment production was studied in five pigment-producing fungi:
Some studies report that the pigment synthesis requires proper aeration probably related to the oxygen dependency of some enzymatic reactions responsible for the production of pigment. In
Carbon and nitrogen are necessary for cellular metabolism, and these sources are related to the formation of biomass, the type produced pigment, and the yield of the desired substance. These nutrients may regulate the expression of genes of interest and activate important metabolic pathways for the production of pigments [45, 58, 59]. In general, glucose, an excellent carbon source for growth, interferes with the formation of many secondary metabolites, including pigments. For example, the pigment production by
Studies have demonstrated that the promoting or repressing effect of a nitrogen source on pigment production is strain dependent. It has been reported that various types of peptone, used as a nitrogen source, are able to promote an increase in the production of pigments in many species of fungi [55, 59, 62, 63]. However,
The optimization of medium composition is an important strategy to increase pigment production because some sources of carbon and nitrogen can be more easily assimilated and promote higher yields of the desired product. During the optimization experiments to enhance the production of melanin by
Since the substrates for the production of pigment strongly influence the cost of the bioprocess, there is a need to select cheap and efficient substrates to make the process economically viable on the industrial scale. Large amounts of agro-industrial residues generated from diverse economic activities have attracted strong industry interest on the utilization of these residues as inexpensive substrates to support the growth of microorganisms in bioprocesses. This strategy may represent an added value to the industry and also helps in solving pollution problems, reducing or preventing their disposal in the environment [1, 66, 67].
Various studies have reported the successful utilization of agro-industrial residues for the production of fungal pigments. The use of corn cob powder as a substrate for production of pigments by
3. Pathways of melanin biosynthesis
Various techniques, including electron paramagnetic resonance [75], X-ray diffraction [76], infrared, ultraviolet and visible spectroscopy [77], and nuclear magnetic resonance [78], have been used to elucidate the melanin structure from different organisms. These studies have shown that fungi can produce different types of melanins by oxidative polymerization of phenolic or indolic compounds [11, 27].
Melanin in cell walls of
In the Ascomycota fungi, melanin pigment is generally synthesized from the pentaketide pathway in which 1,8-dihydroxynaphthalene (DHN) is the immediate precursor of the polymer, as described by Bell and Wheeler [11] based on genetic and biochemical evidence obtained from
However, some species of this class, including
The production of DOPA-melanin has also been investigated in other fungi such as
In this pathway, there are two possible starting molecules, L-dopa and tyrosine. If L-dopa is the precursor molecule, it is oxidized to dopaquinone by laccase. If tyrosine is the precursor, it is first converted to L-dopa and then dopaquinone. The same enzyme, tyrosinase, carries out both steps. Dopaquinone, a highly reactive intermediate, forms leucodopachrome, which is then oxidized to dopachrome. Hydroxylation (and decarboxylation) yields dihydroxyindoles, which can polymerize spontaneously to form DOPA-melanin [10, 27, 97].
Some fungi have more than one biosynthetic pathway of melanins. For example,
The extracellular fungal melanin, which is found in culture fluids usually in the form of granules, can be formed from some culture components, which are autoxidized or are oxidized by phenoloxidases released from the fungus during autolysis [10, 11, 27].
4. Biological activities of melanin
Despite the difference in their origins, melanin pigments have a number of common characteristics that allow them to fulfill their protective function. Several biological functions of melanins are closely associated to their chemical composition and structure. The presence of unpaired electrons in the melanin structure is responsible for various properties, including antioxidant, semiconductor, optical, electronic, and radio- and photoprotective [19].
The effect of melanin enhancing the survival of fungi under adverse conditions is mainly due to its function as an extracellular redox buffer, which can neutralize oxidants generated by the fungus in response to environmental stress [19]. It has been reported that melanin contributes for virulence of
Melanin pigment extracted from several fungal species has shown the ability to scavenge free radicals (reactive nitrogen and oxygen species), becoming a potential natural antioxidant. Melanins produced by
It has been reported that substances acting as antioxidants protect cells from ROS-mediated DNA damage, which can result in mutation and subsequent carcinogenesis. The excess free radicals may attack cellular constituents, as the cell membrane, nucleic acid, protein, enzymes, and other biomolecules, by peroxidation, resulting in the severe damage of cell functions and subsequent serious deleterious effects on the organism [106]. It has been reported that melanin protects melanocytes and keratinocytes from the induction of DNA strand broken by hydrogen peroxide, indicating that this pigment also has an important antioxidant role in the skin [107]. Studies in our laboratory showed that melanin extracted from hyperpigment-productive mutant (MEL1) of
There is experimental evidence that fungal melanin may also act as an anti-aging drug, due to its action in reducing the generation of free radicals, clearing away the free radicals produced in excess, and enhancing the activities of antioxidant enzymes. Studies have shown that one of the major causes of aging is the surplus free radicals produced during the oxidative metabolism in the human body [108]. It was demonstrated that the melanin produced by fungus
Researches have also shown that some fungal melanin exhibits immunomodulatory activity through the inhibition of pro-inflammatory cytokine production in T lymphocytes and monocytes, as well as fibroblasts and endothelial cells [12, 110, 111]. During an inflammatory response, cells of the innate and acquired immune systems release a variety of mediators, such as nitric oxide (NO), tumor necrosis factor-
Some studies have proposed that fungal melanin exhibits anti-radiation activity in vivo and in vivo and then could be explored as a probable radioprotector [16, 115]. Since melanin has a stable free radical population, it is thought that the radioprotective properties of this pigment result from a combination of physical shielding and quenching of cytotoxic free radicals generated by radiation [18]. [116] showed that
Recent studies have demonstrated that, in addition to the ability of transferring electrons arising under the action of radiation, melanin also possesses ionic conductivity due to its ability to transform any type of radiation energy not only into heat but also use it for the maintenance of redox processes in cells [118]. It was assumed that melanin pigments, participating in redox reactions, are able to perceive the energy of radiation (UV, visible light, and radiation) and convert it into useful reducing power for metabolic processes. This hypothesis is supported by the discovery of melanized fungi in soils contaminated by radioactive nuclides and areas around the damaged Chernobyl nuclear reactors, which not only survive high radiation levels but also have enhanced growth upon exposure [16, 19, 119, 120]. Owing to its semiconductor property, melanin becomes a promising material for organic bioelectronic devices like transistors, sensors, and batteries [121].
Fungal melanins also exhibit growth inhibitory effect against various microorganisms. The extracellular melanin isolated from
The anti-cell proliferation effect of fungal melanin in tumoral cell lines has already been demonstrated. [34] reported that the extracellular melanin produced by the fungus
The evaluation of the effect of fungal melanin on non-tumor cells is also interesting because it may serve as alternative to acute in vivo toxicity testing, avoiding the indiscriminate use of animals. The melanin produced by
5. Biotechnological applications of melanin
With the current knowledge about physical and chemical properties and the broad spectrum of biological activities, fungal melanins have attracted growing interest for their potential use in the fields of biomedicine, dermocosmetics, nanotechnology, and materials science.
5.1. Bioelectronic applications
In recent years, the electronics industry has been driven to develop materials and components that are cheaper and more environmentally friendly. As melanin has characteristics of functional materials and bioorganic, a growing number of researchers in the fields of materials science and organic electronics see the melanin with great interest, taking advantage of their properties for applications in organic electronic devices. Melanins present interesting optoelectronic properties, such as high optical absorption in the UV-Vis range, good transmission electronic, and ionic conductivity appreciably, pointing this biomaterial as a promising active component in organic electronic devices with low environmental impact [118, 121, 125–127].
Among the physical properties of melanin, the electrical conductivity is one of the most interesting to investigate in the perspective of technological application. The electrical conductivity properties of this biopolymer are similar to those of amorphous semiconductor solids, and then it can be considered an organic semiconductor, which is largely available and biocompatible and, consequently, cheaper and easier to process with respect to inorganic semiconductors, as silicon germanium. In particular, it can be considered a promising material for sensors and photovoltaic devices, due to broadband spectral absorbance and charge transport properties [128].
The technical literature describes the integration of organic semiconducting polymers as melanin in silicon electronic devices in view of the possibility of achieving multifunctional systems that combine electrical and optical properties of semiconductors, the structural versatility and mechanical characteristics of materials, and processing polymeric [129]. The production of devices based on thin film melanin exhibited electrical conductivity comparable to that of amorphous silicon [130]. In this study, melanin films showed excellent thermal stability and adhere well to glass substrates and silicon, indicating the possibility of using this technique for the production of films from synthetic melanin. Other groups have published various device architectures with applications such as memory (metal-insulator-semiconductor geometries) [131], batteries [132], and biomimetic interfaces [133].
Deposition of homogeneous melanin layers for optoelectronics application is an issue of considerable technological relevance. Synthetic melanin thin films deposited by spray-coating presented features ascribed to an amorphous semiconducting material [134]. They also showed that further improvement of conductivity together with an increased absorption in the NIR region, by doping the synthetic melanin macromolecule, could make this material a good candidate for optical sensing applications. It has been reported that the iron-melanin coating markedly enhances the catalytic activity of the gold nanoparticles (AuNPs) for both the hydrogen peroxide electroreduction and hydrogen evolution reaction [135]. This strategy may be used to improve nanomaterials with potential applications as efficient catalysts and electrocatalysts. Studies have shown that synthetic melanin-like nanoparticles complexed with paramagnetic Fe3+ ions have potential as a highly efficient and nontoxic contrast agent for magnetic resonance imaging instead of Gd3+-based contrast agents, which can cause nephrotoxicity [136].
The optical and electronic properties of melanin have attracted the attention of researchers for the production of continuous thin films from conventional synthetic melanin, which have been used for a number of different device configurations, including chemi-sensors, next-generation solar cells, and a range of other detectors [126, 130, 134]. Potential also exists to use melanin films as an effective radiation sensitizer that could greatly improve the spectral range and efficiency of superconducting transition-edge bolometers [137].
The metal chelation properties of melanin offer interesting possibilities for melanin-based metal ion sensing. A piezoelectric sensor system capable of real-time detection of metal ions was constructed by cross-linking melanin onto the gold electrode of quartz crystal microbalance (QCM) and showed high sensitivity and selectivity to metal ions particularly for Hg(II) [138].
Melanin has many other interesting properties, such as ultraviolet absorption, which has been utilized to prepare optical lenses or filters. Studies have shown that it is possible to use melanin as an ultraviolet, visible and near-infrared absorbing pigment in opthalmic devices, protective eyewear, windows, packaging material, umbrellas, canopies, and other similar media suitable for providing protection from radiation [139, 140]. The incorporation of the melanin in solid plastic films of polyvinyl alcohol (PVA-melanin film system) to be used in conjunction with other plastics to make laminated sheets or lenses, including sunglasses, ski goggles, ophthalmic prescription lenses, helmets, windows, light filters for artificial lighting, and other light filters that protect people from potentially damaging UV and high-energy visible light has also been reported [141].
5.2. Medical applications
Despite its high biocompatibility, the use of melanin as a novel biomaterial in pharmaceutical and biomedical applications reported in literature is still scarce. A study performed with melanin nanoparticles as biocompatible drug nanocarriers, using metronidazole (antibiotic drug), showed that melanin could be a very interesting nanocarrier drug release device because it strongly responds to pH, being a very interesting feature for the treatment of intestine and colon diseases, which would greatly benefit with pH targeting [142]. Another study showed that systemic melanin-covered nanoparticle (MN) administration reduced hematologic toxicity in mice treated with radiation and that these structures provide efficient protection to bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy, permitting the administration to tumors of significantly higher doses [117].
Melanin has also been used to treat various types of malignant cancer tumors, disorders of the immune system including AIDS, diseases of blood origin and disorders due to the disturbances in cell homeostasis, and complex and hardly curable mental disorders (schizophrenia, epilepsy) involving nervous and other regulatory systems. A study on the use of melanin for the treatment of Parkinson’s disease, an amelioration in the monkeys’ overall functional ability and secondary motor manifestations by the administration of an effective amount of melanin in monkeys treated with MPTP (1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine), a toxin that causes a neurodegenerative disease, was observed. This study demonstrated that toxin-induced Parkinson’s disease could be prevented in the melanin-treated animals because the administered melanin causes chelation or scavenging of toxins, such as MPTP, thus preventing a neurodegenerative disease, such as Parkinson’s disease. The results of this study also showed that melanin administration to aid the recovery of neurons in a mammal having neuron injury suggests that melanin can be used to treat Alzheimer’s disease [143].
Owing to their ability to increase the permeability of the blood-brain barrier, the melanin is also useful as carriers for other therapeutic agents, which must reach brain tissue to produce their therapeutic responses [144]. Two examples of such therapeutic agents that will cross the blood-brain barrier when linked to melanin are boron and nerve growth factor. According to the same authors, the melanin is also an effective vehicle for the transport of boron to cancerous sites in the body, mainly when the cancerous cells to be treated are located in the brain, because this pigment binds boron very strongly. The melanin can also function as a carrier for nerve growth factor due to the ability to get nerve growth factor across the blood-brain barrier, and this is the major advantage over conventional therapy.
In recent years, efforts have been focused on investigating the potential use of this pigment as active material in tissue repair engineering. Bettinger et al. [145] reported that thin films of melanin were found to enhance Schwann cell growth and neurite extension in rat pheochromocytoma cells (PC12 cells) compared to collagen films in vitro. Melanin films also induced an inflammation response that was comparable to silicone implants in vivo, and the implants were significantly resorbed after 8 weeks. These results showed that melanin thin films have great potential in the reconstruction of tissues, being biodegradable, and possess inflammatory response comparable to silicone. Another study of the biocompatibility of melanin thin films demonstrated that the melanin film effectively supports the growth of undifferentiated stem cells and their differentiation into neuronal precursors and neurons [146]. They related that high-quality melanin thin films display appealing features, such as reversible conductivity by controlled hydration—dehydration steps—excellent biocompatibility with stem cells, and water-resistant adhesion, for bioelectronic applications, e.g., in organic electrochemical transistors (OECTs), which can translate cellular activity into electrical signals [125, 147]. It has also been reported that melanin thin films possess highly desirable physical and biological properties that make them ideal for organic bioelectronic devices [130].
In cosmetic industry, there are great interests in the melanin, especially to protect against the noxious effects of UV radiation by incorporation in skin photoprotection formulations [35, 148]. The protective action of melanin is related to its high efficiency to absorb and scatter photons, particularly the higher-energy photons from the UV and blue part of the solar spectrum. Very likely, melanin photoprotection is also due to its ability to quench excited states of certain molecules and scavenge ROS that may be generated in pigmented cells [126]. Development of methods for producing melanin soluble in aqueous cosmetic buffers at physiological pH and temperature may make possible the use of this pigment as ingredients of face and hand creams, lotions, antiaging ointments, or foundation makeups, acting as a screen and antioxidant for the protection against photoinduced skin damages [149]. Other dermocosmetic applications of melanins include the use of the pigment for hair dyeing and the development of novel strategies for hair recoloration [150].
Since melanin has a stable free radical population, it is thought that the radioprotective properties of this pigment result from a combination of physical shielding and quenching of cytotoxic free radicals generated by radiation [18]. Some studies suggest the possible use of melanin-coated nanoparticles in medicine, mainly for protecting patients against the harmful effects of gamma rays during radioimmunotherapy [34, 151]. Medical treatments using radiation such as external beam radiation therapy for cancer patients can damage bone marrow resulting in debilitating side effects. In experimental models, melanin can successfully shield bone marrow from such side effects. Mice treated with melanin-coated nanoparticles have higher white blood cell and platelet counts than control mice after radiation treatment [117]. It has been reported the use of melanin, a biopolymer with good biocompatibility and biodegradability, intrinsic photo-acoustic properties, binding ability to drugs, and chelating property to radioactive metal ions, as an efficient endogenous nanosystem for imaging-guided chemotherapy [152]. According to the authors, melanin nanoparticles could successfully enter into the tumor and act as an efficient drug-delivery system, thereby greatly increasing the safe utility of the drugs for tumor treatment and significantly lowering the dosage used and its side effects.
A valuable biotechnological approach to the melanin-mediated synthesis of silver nanostructures with broad-spectrum antimicrobial activity has been developed. Silver nanostructures synthesized with melanin derived from
5.3. Environmental applications
The chemical structure of melanin presents many oxygen-containing groups, including carboxyl, phenolic and alcoholic hydroxyl, carbonyl, and methoxy groups, which have the ability to bind to a broad spectrum of substances [153]. In literature, studies have confirmed that fungal melanin acts as metal chelators, enhancing the biomass-metal interaction and consequently its biosorption capacity [14]. Study conducted by [154] showed that a melanin-rich strain of the fungus
Some melanized fungi have shown to be good candidates for bioremediation of contaminated sites, due to the ability of fungal melanin to bind to heavy metals and radionuclides in contaminated sites. Experimental evidence shows that the accumulation of 90Sr by conidia or mycelium by a range of microfungal species is greater in pigmented than in unpigmented species [158]. [159] In a study on the uptake efficiency of the radiocesium (137Cs) and radiocobalt (60Co) in melanized and nonmelanized fungi, it was observed that 60% of both radionuclides were uptaken by melanin of
6. Conclusion
Melanin possesses physicochemical properties and biological activities that make it a suitable biomaterial for a wide range of applications in cosmetic, pharmaceutical, electronic, and food processing industries. In addition, this pigment has a considerable interest biotechnological because it can be produced on a large scale with low cost, making its use for future practical applications economically advantageous. However, it is necessary to expand the knowledge about the structure-property-function relationships for the development of melanin-based technology. In the context, we hope that the information in this book will be useful and will encourage a greater number of researches on fungal melanin, which might be useful to deploy innovative and sustainable solutions for human health and the environment.
References
- 1.
Lopes FC, Tichota DM, Pereira JQ, Segalin J, De Oliveira Rios A, Brandelli A. Pigment production by filamentous fungi on agro-industrial byproducts: An eco-friendly alternative. Appl Biochem Biotechnol. 2013;171(3):616–625. - 2.
Demain AL. Importance of microbial natural products and the need to revitalize their discovery. J Ind Microbiol Biotechnol. 2014;41(2):185–201. - 3.
Kirti K, Amita S, Priti S, Kumar AM, Jyoti S. Colorful world of microbes: Carotenoids and their applications. Adv Biol. 2014;2014(1):1–13. - 4.
Kumar A, Vishwakarma HS, Singh J, Kumar M. Microbial pigments: Production and their applications in various industries. Int J Pharm Chem Biol Sci. 2015;5(1):203–212. - 5.
Panesar R, Kaur S, Panesar PS. Production of microbial pigments utilizing agro-industrial waste: A review. Curr Opin Food Sci 2015;1:70–76. Available from: http://dx.doi.org/10.1016/j.cofs.2014.12.002 - 6.
Akilandeswari P, Pradeep BV. Exploration of industrially important pigments from soil fungi. Appl Microbiol Biotechnol. 2016;100(4):1631–1643. - 7.
Duran N, Teixeira MF, De Conti R, Esposito E Ecological-friendly pigments fungi. Critic Rev Food Sci Nutr. 2002;42(1):53–66. - 8.
Dufossé L, Fouillaud M, Caro Y, Mapari SAS, Sutthiwong N. Filamentous fungi are large-scale producers of pigments and colorants for the food industry. Curr Opin Biotechnol. 2014;26:56–61. - 9.
Chambergo FS, Valencia EY. Fungal biodiversity to biotechnology. Appl Microbiol Biotechnol. 2016;100(6):2567–2577. - 10.
Butler MJ, Day AW. Fungal melanins: A review. Can J Microbiol. 1998;44(12):1115–1136. - 11.
Bell AA, Wheeler MH. Biosynthesis and functions of fungal melanins. Annu Rev Phytopathol. 1986;24:411–451. - 12.
Plonka PM, Grabacka M. Melanin synthesis in microorganisms – biotechnological and medical aspects. Acta Biochim Pol. 2006;53(3):429–443. - 13.
Eisenman HC, Casadevall A. Synthesis and assembly of fungal melanin. Appl Microbiol Biotechnol. 2012;93(3):931–940. - 14.
Fogarty RV, Tobin JM. Fungal melanins and their interaction with metals. Enzyme Microb Technol. 1996;19(June 1995):317. - 15.
García-Rivera J, Casadevall A. Melanization of Cryptococcus neoformans reduces its susceptibility to the antimicrobial effects of silver nitrate. Med Mycol. 2001;39(October 2000):353–357. - 16.
Dadachova E, Bryan RA, Huang X, Moadel T, Schweitzer AD, Aisen P, et al.. Ionizing radiation changes the electronic properties of melanin and enhances the growth of melanized fungi. PLoS One. 2007;2(5):1–13. - 17.
Gómez BL, Nosanchuk JD. Melanin and fungi. Curr Opin Infect Dis. 2003;16(2):91–96. - 18.
Dadachova E, Bryan RA, Howell RC, Schweitzer AD, Aisen P, Nosanchuk JD, et al.. The radioprotective properties of fungal melanin are a function of its chemical composition, stable radical presence and spatial arrangement. Pigment Cell Melanoma Res. 2008;21(2):192–199. - 19.
Gessler NN, Egorova AS, Belozerskaya TA. Melanin pigments of fungi under extreme environmental conditions (Review). Appl Biochem Microbiol. 2014;50(2):105–113. - 20.
Schnitzler N, Peltroche-Llacsahuanga H, Bestier N, Zündorf J, Lütticken R, Haase G. Effect of melanin and carotenoids of Exophiala (Wangiella) dermatitidis on phagocytosis, oxidative burst, and killing by human neutrophils. Infect Immun. 1999;67(1):94–101. - 21.
Romero-Martinez R, Wheeler M, Guerrero-Plata A, Rico G, Torres-Guerrero H. Biosynthesis and functions of melanin in Sporothrix schenckii . Infect Immun. 2000;68(6):3696–3703. - 22.
Nosanchuk JD, Stark RE, Casadevall A. Fungal melanin: What do we know about structure? Front Microbiol. 2015;6:1–7. - 23.
Doering TL, Nosanchuk JD, Roberts WK, Casadevall A. Melanin as a potential cryptococcal defence against microbicidal proteins. Med Mycol. 1999;37(3):175–181. - 24.
Casadevall A, Rosas AL, Nosanchuk JD. Melanin and virulence in Cryptococcus neoformans . Curr Opin Microbiol. 2000;3(4):354–358. - 25.
Rosas ÁL, Casadevall A. Melanization decreases the susceptibility of Cryptococcus neoformans to enzymatic degradation. Mycopathologia. 2001;151(2):53–56. - 26.
Paolo WF, Dadachova E, Mandal P, Casadevall A, Szaniszlo PJ, Nosanchuk JD. Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature. BMC Microbiol. 2006;6:55. - 27.
Langfelder K, Streibel M, Jahn B, Haase G, Brakhage AA. Biosynthesis of fungal melanins and their importance for human pathogenic fungi. Fungal Genet Biol. 2003;38(2):143–158. - 28.
Nosanchuk JD, Casadevall A. The contribution of melanin to microbial pathogenesis. Cell Microbiol. 2003;5(4):203–223. - 29.
Wang Y, Casadevall A. Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants. Infect Immun. 1994;62(7):3004–3007. - 30.
Jacobson ES, Hove E, Emery HS. Antioxidant function of melanin in black fungi. Infect Immun. 1995;63(12):4944–4945. - 31.
Goncalves CRR, Pombeiro-Sponchiado SR. Antioxidant activity of the melanin pigment extracted from Aspergillus nidulans . Biol Pharm Bull. 2005;28(6):1129–1131. - 32.
Gonçalves R de CR, Kitagawa RR, Raddi MSG, Carlos IZ, Pombeiro-Sponchiado SR. Inhibition of nitric oxide and tumour necrosis factor-α production in peritoneal macrophages by Aspergillus nidulans melanin. Biol Pharm Bull. 2013;36(12):1915–1920. - 33.
Kunwar A, Adhikary B, Jayakumar S, Barik A, Chattopadhyay S, Raghukumar S, et al.. Melanin, a promising radioprotector: Mechanisms of actions in a mice model. Toxicol Appl Pharmacol. 2012;264(2):202–211. - 34.
Arun G, Eyini M, Gunasekaran P. Characterization and biological activities of extracellular melanin produced by Schizophyllum commune (Fries). Indian J Exp Biol. 2015;53(6):380–387. - 35.
d’Ischia M, Wakamatsu K, Cicoira F, Di Mauro E, Garcia-Borron JC, Commo S, et al.. Melanins and melanogenesis: From pigment cells to human health and technological applications. Pigment Cell Melanoma Res. 2015;28(5):520–544. - 36.
Demain AL, Adrio JL. Strain improvement for production of pharmaceuticals and other microbial metabolites by fermentation. Nat Compd Drugs. 2008;1:251–289. - 37.
Babitha S. Microbial Pigments. In: Nigam PSN, Pandey A, editors. Biotechnology for agro-industrial residues utilization: utilization of agro-residues. Netherlands: Springer; 2009. p. 147–162. - 38.
Meyer V, Wu B, Ram AFJ. Aspergillus as a multi-purpose cell factory: Current status and perspectives. Biotechnol Lett. 2011;33(3):469–476. - 39.
Mapari SAS, Nielsen KF, Larsen TO, Frisvad JC, Meyer AS, Thrane U. Exploring fungal biodiversity for the production of water-soluble pigments as potential natural food colorants. Curr Opin Biotechnol. 2005;16(2):231–238. - 40.
Mapari SA, Meyer AS, Thrane U, Frisvad JC. Identification of potentially safe promising fungal cell factories for the production of polyketide natural food colorants using chemotaxonomic rationale. Microb Cell Fact. 2009;8:24. - 41.
Dikshit R, Tallapragada P. Monascus purpureus : A potential source for natural pigment production. J Microbiol Biotechnol Res. 2011;1(4):164–174. - 42.
Marova I, Carnecka M, Halienova A, Certik M, Dvorakova T, Haronikova A. Use of several waste substrates for carotenoid-rich yeast biomass production. J Environ Manage. 2012;95(Suppl.):S338–S342. - 43.
Sharmila G, Nidhi B, Muthukumaran C. Sequential statistical optimization of red pigment production by Monascus purpureus (MTCC 369) using potato powder. Ind Crops Prod. 2013;44:158–164. - 44.
Prajapati VS, Soni N, Trivedi UB, Patel KC. An enhancement of red pigment production by submerged culture of Monascus purpureus MTCC 410 employing statistical methodology. Biocatal Agric Biotechnol. 2014;3(2):140–145. - 45.
Hajjaj H, Goma G, François JM. Effect of the cultivation mode on red pigments production from Monascus ruber . Int J Food Sci Technol. 2015;50(8):1–6. - 46.
Zhang M, Xiao G, Thring RW, Chen W, Zhou H, Yang H. Production and characterization of melanin by submerged culture of culinary and medicinal fungi Auricularia auricula . Appl Biochem Biotechnol. 2015;176(1):253–266. - 47.
da Costa Souza PN, Grigoletto TLB, de Moraes LAB, Abreu LM, Guimarães LHS, Santos CR, et al.. Production and chemical characterization of pigments in filamentous fungi. Microbiology. 2015;162:12–22. - 48.
Joshi VK, Attri D, BaJa A, Bhushan S. Microbial pigments. Indian J Biotechnol. 2003;2(Aug):362–369. - 49.
Ahn J, Jung J, Hyung W, Haam S, Shin C. Enhancement of Monascus pigment production by the culture ofMonascus sp. J101 at low temperature. Biotechnol Prog. 2006;22(1):338–340. - 50.
Lisboa HCF.Influence of culture conditions on the production of melanin pigment by Aspergillus fungus [thesis]. Araraquara: Sao Paulo State University; 2003. - 51.
Orozco SFB, Kilikian BV. Effect of pH on citrinin and red pigments production by Monascus purpureus CCT3802. World J Microbiol Biotechnol. 2008;24(2):263–268. - 52.
Kang B, Zhang X, Wu Z, Wang Z, Park S. Production of citrinin-free Monascus pigments by submerged culture at low pH. Enzyme Microb Technol. 2014;55:50–57. - 53.
Tudor D, Robinson SC, Cooper PA. The influence of pH on pigment formation by lignicolous fungi. Int Biodeterior Biodegrad. 2013;80:22–28. - 54.
Méndez A, Pérez C, Montañéz JC, Martínez G, Aguilar CN. Red pigment production by Penicillium purpurogenum GH2 is influenced by pH and temperature. J Zhejiang Univ Sci B. 2011;12(12):961–968. - 55.
Velmurugan P, Lee YH, Venil CK, Lakshmanaperumalsamy P, Chae JC, Oh BT. Effect of light on growth, intracellular and extracellular pigment production by five pigment-producing filamentous fungi in synthetic medium. J Biosci Bioeng. 2010;109(4):346–350. - 56.
Zhou Z, Yin Z, Hu X. Corncob hydrolysate, an efficient substrate for Monascus pigment production through submerged fermentation. Biotechnol Appl Biochem. 2014;61(6):716–723. - 57.
Said FM, Chisti Y, Brooks J, The effects of forced aeration and initial moisture level on red pigment and biomass production by Monascus ruber in packed bed solid state fermentation. Int J Environ Sci Dev. 2010;1(1):1–4. - 58.
Ruiz B, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, et al.. Production of microbial secondary metabolites: Regulation by the carbon source. Crit Rev Microbiol. 2010;36(2):146–167. - 59.
Pradeep FS, Begam MS, Palaniswamy M, Pradeep BV. Influence of culture media on growth and pigment production by Fusarium moniliforme KUMBF1201 isolated from paddy field soil. World Appl Sci J. 2013;22(1):70–77. - 60.
Gunasekaran S, Poorniammal R. Optimization of fermentation conditions for red pigment production from Penicillium sp. under submerged cultivation. Afr J Biotechnol. 2008;7(12):1894–1898. - 61.
nee’Nigam PS. Production of bioactive secondary metabolites. In: Nigam PSN, Pandey A, editors. Biotechnology for agro-industrial residues utilization: utilization of agro-residues. Netherlands: Springer; 2009. p. 129-145. - 62.
Quereshi S, Pandey AK, Singh J. Optimization of fermentation conditions for red pigment production from Phoma herbarum (FGCC# 54) under submerged cultivation. J Phytol. 2010;2(9). - 63.
Celestino JR, de Carvalho LE, da Paz Lima, M, Lima AM, Ogusku MM, de Souza JVB. Bioprospecting of Amazon soil fungi with the potential for pigment production. Process Biochem. 2014;49(4):569–575. - 64.
Jalmi P, Bodke P, Wahidullah S, Raghukumar S. The fungus Gliocephalotrichum simplex as a source of abundant, extracellular melanin for biotechnological applications. World J Microbiol Biotechnol. 2012;28(2):505–512. - 65.
Sun S, Zhang X, Chen W, Zhang L, Zhu H. Production of natural edible melanin by Auricularia auricula and its physicochemical properties. Food Chem. 2016;196:486–492. - 66.
Pandey A, Soccol CR, Mitchell D. New developments in solid state fermentation: I-bioprocesses and products. Process Biochem. 2000;35(10):1153–1169. - 67.
Singhania RR, Soccol CR, Pandey A. Application of tropical agro-industrial residues as substrate for solid-state fermentation processes. In: Pandey A, Soccol CR, Larroche C, editors. Current developments in solid-state fermentation. New York: Springer; 2008. p. 412–442. - 68.
Velmurugan P, Hur H, Balachandar V, Kamala-Kannan S, Lee KJ, Lee SM, Chae JC, Oh BT. Monascus pigment production by solid-state fermentation with corn cob substrate. J Biosci Bioeng. 2011;112(6):590–594. - 69.
Babitha S, Soccol CR, Pandey A Jackfruit seed-a novel substrate for the production of Monascus pigments through solid-state fermentation. Food Technol Biotechnol. 2006;44(4):465–471. - 70.
Hamano PS, Kilikian BV. Production of red pigments by Monascus ruber in culture media containing corn steep liquor. Brazilian J Chem Eng. 2006;23(4):443–449. - 71.
Silveira ST, Daroit DJ, Brandelli A. Pigment production by Monascus purpureus in grape Waste using factorial design. LWT – Food Sci Technol. 2008;41(1):170–174. - 72.
Rani MHS, Ramesh T, Subramanian J, Kalaiselvam M. Production and characterization of melanin pigment from halophilic black yeast Hortaea werneckii . Int J Pharma Res Rev. 2013;2(8):9–17. - 73.
Zou Y, Tian M. Fermentative production of melanin by Auricularia auricula . J Food Process Preserv. 2016;0:0–5. - 74.
Pretti TS. Optimization of the culture conditions of Aspergillus nidulans fungus for the production of melanin using agroindustrial residues [thesis]. Araraquara: Sao Paulo State University, 2009. - 75.
Enochs WS, Nilges MJ, Swartz HM. A standardized test for the identification and characterization of melanins using electron paramagnetic resonance (EPR) spectroscopy. Pigment Cell Res. 1993;6(2):91–99. - 76.
Crippa R, Horak V, Prota G, Svoronos P, Wolfram L. Chemistry of melanins alkaloids. Chem Pharmacol. 1990;36:253–323. - 77.
Wilczok T, Bilińska B Buszman E, Kopera M. Spectroscopic studies of chemically modified synthetic melanins. Arch Biochem Biophys. 1984;231(2):257–262. - 78.
Duff GA, Roberts JE, Foster N. Analysis of the structure of synthetic and natural melanins by solid-phase NMR. Biochemistry. 1988;27(18):7112–7116. - 79.
Piattelli M, Fattorusso E, Nicolaus RA, Magno S. The structure of melanins and melanogenesis—V: Ustilagomelanin. Tetrahedron. 1965;21(11):3229–3236. - 80.
Stüssi H, Rast DM. The biosynthesis and possible function of γ-glutaminyl-4-hydroxybenzene in Agaricus bisporus . Phytochemistry. 1981;20(10):2347–2352. - 81.
Eisenman HC, Mues M, Weber SE, Frases S, Chaskes S, Gerfen G, Casadevall A. Cryptococcus neoformans laccase catalyses melanin synthesis from both D-and L-DOPA. Microbiology. 2007;153(12):3954–3962. - 82.
Frases S, Salazar A, Dadachova E, Casadevall A Cryptococcus neoformans can utilize the bacterial melanin precursor homogentisic acid for fungal melanogenesis. Appl Environ Microbiol. 2007;73(2):615–621. - 83.
Garcia-Rivera J, Eisenman HC, Nosanchuk JD, Aisen P, Zaragoza O, Moadel T, et al.. Comparative analysis of Cryptococcus neoformans acid-resistant particles generated from pigmented cells grown in different laccase substrates. Fungal Genet Biol. 2005;42(12):989–998. - 84.
Geis PA, Wheeler MH, Szaniszlo PJ. Pentaketide metabolites of melanin synthesis in the dematiaceous fungus Wangiella dermatitidis . Arch Microbiol. 1984;137(4):324–328. - 85.
Wheeler MH, Stipanovic RD. Melanin biosynthesis and the metabolism of flaviolin and 2-hydroxyjuglone in Wangiella dermatitidis . Arch Microbiol. 1985;142(3):234–241. - 86.
Saiz-Jimenez C. Microbial melanins in stone monuments. Sci Total Environ. 1995;167(1):273–286. - 87.
Henson JM, Butler MJ, Day AW. The dark side of the mycelium: Melanins of phytopathogenic fungi. Annu Rev Phytopathol. 1999;37(1):447–471. - 88.
Wu Y, Shan L, Yang S, Ma A. Identification and antioxidant activity of melanin isolated from Hypoxylon archeri , a companion fungus ofTremella fuciformis . J Basic Microbiol. 2008;48(3):217–221. - 89.
Bull AT. Chemical composition of wild-type and mutant Aspergillus nidulans cell walls. The nature of polysaccharide and melanin constituents. J Gen Microbiol. 1970;63(1):75–94. - 90.
Rowley BI, Pirt SJ. Melanin production by Aspergillus nidulans in batch and chemostat cultures. Microbiology. 1972;72(3):553–563. - 91.
Bull AT, Carter BLA. The isolation of tyrosinase from Aspergillus nidulans , its kinetic and molecular properties and some consideration of its activity in vivo. Microbiology. 1973;75(1):61–73. - 92.
Martinelli SD, Bainbridge BW. Phenoloxidases of Aspergillus nidulans . Trans Br Mycol Soc. 1974;63(2):361–370. - 93.
Gonçalves RCR, Lisboa HCF, Pombeiro-Sponchiado SR. Characterization of melanin pigment produced by Aspergillus nidulans . World J Microbiol Biotechnol. 2012;28(4):1467–1474. - 94.
Fling M, Horowitz NH, Heinemann SF. The isolation and properties of crystalline tyrosinase from Neurospora . J Biol Chem. 1963;238(6):2045–2053. - 95.
Esser K. Phenoloxidases in the ascomycete Podospora anserina . I. The identification of laccase and tyrosinase in the wild strain. Arch Mikrobiol. 1963;46:217–226. - 96.
Williamson PR, Wakamatsu K, Ito S. Melanin biosynthesis in Cryptococcus neoformans . J Bacteriol. 1998;180(6):1570–1572. - 97.
Prota G. Melanins and Melanogenesis. Academic Press, San Diego, CA; 1992. - 98.
Tsai HF, Fujii I, Watanabe A, Wheeler MH, Chang YC, Yasuoka Y, Ebizuka Y, Kwon-Chung KJ. Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptaketide precursor. J Biol Chem. 2001;276(31):29292–29298. - 99.
Schmaler-Ripcke J, Sugareva V, Gebhardt P, Winkler R, Kniemeyer O, Heinekamp T, Brakhage AA. Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus . Appl Environ Microbiol. 2009;75(2):493–503. - 100.
Jolivet S, Arpin N, Wichers HJ, Pellon G. Agaricus bisporus browning: A review. Mycol Res. 1998;102(12):1459–1483. - 101.
Gessler NN, Aver’yanov AA, Belozerskaya TA. Reactive oxygen species in regulation of fungal development. Biochemistry. 2007;72(10):1091–1109. - 102.
Zhan F, He Y, Zu Y, Li T, Zhao Z. Characterization of melanin isolated from a dark septate endophyte (DSE), Exophiala pisciphila , World J Microbiol Biotechnol. 2011;27(10):2483–2489. - 103.
Kumar CG, Mongolla P, Pombala S, Kamle A, Joseph J. Physicochemical characterization and antioxidant activity of melanin from a novel strain of Aspergillus bridgeri ICTF-201. Lett Appl Microbiol. 2011;53(3):350–358. - 104.
Cunha MML, Franzen AJ, Seabra SH, Herbst MH, Vugman NV, Borba LP, Souza W, Rozental S. Melanin in Fonsecaea pedrosoi: A trap for oxidative radicals. BMC Microbiol. 2010;10(1):1–9. - 105.
Dong C, Yao Y. Isolation, characterization of melanin derived from Ophiocordyceps sinensis , an entomogenous fungus endemic to the Tibetan Plateau. J Biosci Bioeng. 2012;113(4):474–479. - 106.
Lopaczynski W, Zeisel SH. Antioxidants, programmed cell death, and cancer. Nutr Res. 2001;21(1):295–307. - 107.
Hoogduijn MJ, Cemeli E, Anderson D, Wood JM, Thody AJ. Melanin protects against Ho-induced DNA strand breaks through its ability to bind Ca. Br J Dermatol. 2003;148(4):867. - 108.
Harman D. Free radical theory of aging: An update. Ann N Y Acad Sci. 2006;1067(1):10–21. - 109.
Lu Y, Ye M, Song S, Li L, Shaikh F, Li J. Isolation, purification, and anti-aging activity of melanin from Lachnum singerianum . Appl Biochem Biotechnol. 2014;174(2):762–771. - 110.
Mohagheghpour N, Waleh N, Garger SJ, Dousman L, Grill LK, Tusé D. Synthetic melanin suppresses production of proinflammatory cytokines. Cell Immunol. 2000;199(1):25–36. - 111.
Mednick AJ, Nosanchuk JD, Casadevall A. Melanization of Cryptococcus neoformans affects lung inflammatory responses during cryptococcal infection. Infect Immun. 2005;73(4):2012–2019. - 112.
Cruvinel WDM, Mesquita Júnior D, Araújo JAP, Catelan TTT, Souza AWSD, Silva NPD, Andrade LEC. Immune system: Part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response. Revista brasileira de reumatologia. 2010; 50(4):434–447. - 113.
Bocca AL, Brito PP, Figueiredo F, Tosta CE. Inhibition of nitric oxide production by macrophages in chromoblastomycosis: A role for Fonsecaea pedrosoi melanin. Mycopathologia. 2006;161(4):195–203. - 114.
Zhang J, Wang L, Xi L, Huang H, Hu Y, Li X, Huang X, Lu S, Sun J. Melanin in a meristematic mutant of Fonsecaea monophora inhibits the production of nitric oxide and Th1 cytokines of murine macrophages. Mycopathologia. 2013;175(5–6):515–522. - 115.
Schweitzer AD, Howell RC, Jiang Z, Bryan RA, Gerfen G, Chen CC, Mah D, Cahill S, Casadevall A, Dadachova E. Physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors. PLoS One. 2009;4(9):1–8. - 116.
Ye M, Guo G, Lu Y, Song S, Wang HY, Yang L. Purification, structure and anti-radiation activity of melanin from Lachnum YM404. Int J Biol Macromol. 2014;63(1):170–176. - 117.
Schweitzer AD, Revskaya E, Chu P, Pazo V, Friedman M, Nosanchuk JD, Cahill S, Frases S, Casadevall A, Dadachova E. Melanin-covered nanoparticles for protection of bone marrow during radiation therapy of cancer. Int J Radiat Oncol Biol Phys. 2010;78(5):1494–1502. - 118.
Mostert AB, Powell BJ, Pratt FL, Hanson GR, Sarna T, Gentle IR, Meredith P. Role of semiconductivity and ion transport in the electrical conduction of melanin. Proc Natl Acad Sci. 2012;109(23):8943–8947. - 119.
Mironenko NV, Alekhina IA, Zhdanova NN, Bulat SA. Intraspecific variation in gamma-radiation resistance and genomic structure in the filamentous fungus Alternaria alternata : A case study of strains inhabiting Chernobyl Reactor No. 4. Ecotoxicol Environ Saf. 2000;45(2):177–187. - 120.
Dighton J, Tugay T, Zhdanova N. Fungi and ionizing radiation from radionuclides. FEMS Microbiol Lett. 2008;281(2):109–120. - 121.
Mostert AB, Powell BJ, Gentle IR, Meredith P. On the origin of electrical conductivity in the bio-electronic material melanin. Appl Phys Lett. 2012;100(9). - 122.
Bin L, Wei L, Xiaohong C, Mei J, Mingsheng D. In vitro antibiofilm activity of the melanin from Auricularia auricula , an edible jelly mushroom. Ann Microbiol. 2012;62(4):1523–1530. - 123.
Apte M, Girme G, Bankar A, Ravikumar A, Zinjarde S. 3,4-dihydroxy-L-phenylalanine-derived melanin from Yarrowia lipolytica mediates the synthesis of silver and gold nanostructures. J Nanobiotechnol. 2013;3–11. - 124.
Kiran GS, Dhasayan A, Lipton AN, Selvin J, Arasu MV, Al-Dhabi NA. Melanin-templated rapid synthesis of silver nanostructures. J Nanobiotechnol. 2014;12(1):18. - 125.
Goncalves PJ, Baffa O, Graeff CFO, Gonçalves PJ, Filho OB. Effects of hydrogen on the electronic properties of synthetic melanin. J Appl Phys. 2006;99(10):104701. - 126.
Meredith P, Sarna T. The physical and chemical properties of eumelanin. Pigment Cell Res. 2006;19(6):572–594. - 127.
Ambrico M, Ambrico PF, Ligonzo T, Cardone A, Cicco SR, d’Ischia M, Farinola GM. From commercial tyrosine polymers to a tailored polydopamine platform: Concepts, issues and challenges en route to melanin-based bioelectronics. J Mater Chem C. 2015;3(25):6413–6423. - 128.
Ligonzo T, Ambrico M, Augelli V, Perna G, Schiavulli L, Tamma MA, et al.. Electrical and optical properties of natural and synthetic melanin biopolymer. J Non Cryst Solids. 2009;355(22–23):1221–1226. - 129.
Ambrico M, Ambrico PF, Cardone A, Ligonzo T, Cicco SR, Di Mundo R, et al.. Melanin layer on silicon: An attractive structure for a possible exploitation in bio-polymer based metal-insulator-silicon devices. Adv Mater. 2011;23(29):3332–3336. - 130.
Bothma JP, de Boor J, Divakar U, Schwenn PE, Meredith P. Device‐quality electrically conducting melanin thin films. Adv Mater. 2008;20(18):3539–3542. - 131.
Ambrico M, Ambrico PF, Ligonzo T, Cardone A, Cicco SR, Lavizzera A, et al.. Memory-like behavior as a feature of electrical signal transmission in melanin-like bio-polymers. Appl Phys Lett. 2012;100(25). - 132.
Kim YJ, Wu W, Chun SE, Whitacre JF, Bettinger CJ. Biologically derived melanin electrodes in aqueous sodium-ion energy storage devices. Proc Natl Acad Sci. 2013;110(52):20912–20917. - 133.
Ambrico M, Ambrico PF, Cardone A, Cicco SR, Palumbo F, Ligonzo T, Mundo RD, Petta V, Augelli V, Favia P, Farinola GM. Melanin-like polymer layered on a nanotextured silicon surface for a hybrid biomimetic interface. J Mater Chem C. 2014;2(3):573–582. - 134.
Morresi L, Ficcadenti M, Pinto N, Murri R, Cuccioloni M, Angeletti M, et al.. Optical and electrical behavior of synthetic melanin thin films spray-coated. Energy Procedia. 2010;2(1):177–182. - 135.
Orive AG, Grumelli D, Vericat C, Ramallo-López JM, Giovanetti L, Benitez G, et al.. “Naked” gold nanoparticles supported on HOPG: Melanin functionalization and catalytic activity. Nanoscale. 2011;3(4):1708. - 136.
Ju KY, Lee JW, Im GH, Lee S, Pyo J, Park SB, Lee JH, Lee JK. Bio-inspired, melanin-like nanoparticles as a highly efficient contrast agent for T1-weighted magnetic resonance imaging. Biomacromolecules. 2013;14(10):3491–3497. - 137.
Seppä H. Superconducting transition-edge bolometer in a resistive and in an inductive mode. IEEE Trans Appl Supercond. 2001;11(1):759–761. - 138.
Huang GS, Wang M Te, Su CW, Chen YS, Hong MY. Picogram detection of metal ions by melanin-sensitized piezoelectric sensor. Biosens Bioelectron. 2007;23(3):319–325. - 139.
Gallas JM. Optical lens system incorporating melanin as an absorbing pigment for protection against electromagnetic radiation. Patent No. 4,698,374, 1987. - 140.
Gallas JM. Medium incorporating melanin as an absorbing pigment for protection against electromagnetic radiation. Patent No. 5,047,447, 1991. - 141.
Gallas J, Eisner M. Melanin polyvinyl alcohol plastic laminates for optical applications. Patent No. 7,029,758, 2006. - 142.
Araújo M, Viveiros R, Correia TR, Correia IJ, Bonifácio VDB, Casimiro T, et al.. Natural melanin: A potential pH-responsive drug release device. Int J Pharm. 2014;469(1):140–145. - 143.
Berliner DL, Erwin RL, McGee DR. Therapeutic uses of melanin. Patent No. 5,776,968, 1998. - 144.
Berliner DL, Erwin RL, McGee DR. Methods of treating Parkinson’s disease using melanin. Patent No. 5,210,076, 1993. - 145.
Bettinger CJ, Bruggeman JP, Misra A, Borenstein JT, Langer R. Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering. Biomaterials. 2009;30(17):3050–3057. - 146.
Pezzella A, Barra M, Musto A, Navarra A, Alfè M, Manini P, et al.. Stem cell-compatible eumelanin biointerface fabricated by chemically controlled solid state polymerization. Mater Horiz. 2015;2(2):212–220. - 147.
Rivnay J,Owens RM,Malliaras GG. The rise of organic bioelectronics. Chemistry of Materials. 2013;26(1):679-685. - 148.
Solano F. Melanins: Skin pigments and much more—types, structural models, biological functions, and formation routes. New J Sci. 2014; 2014:1–28. - 149.
Pawelek JM, Platt JT. Cosmetic melanins. Patent No. 5,744,125, 1998. - 150.
D’Ischia M, Wakamatsu K, Napolitano A, Briganti S, Garcia-Borron JC, Kovacs D, et al.. Melanins and melanogenesis: Methods, standards, protocols. Pigment Cell Melanoma Res. 2013;26(5):616–633. - 151.
Kunwar A, Adhikary B, Jayakumar S, Barik A, Chattopadhyay S,Raghukumar S, Priyadarsini KI. Melanin, a promising radioprotector: Mechanisms of actions in a mice model. Toxicol Appl Pharmacol. 2012;264(2):202–211. - 152.
Zhang R, Fan Q, Yang M, Cheng K, Lu X, Zhang L, et al.. Engineering melanin nanoparticles as an efficient drug-delivery system for imaging-guided chemotherapy. Adv Mater. 2015;27(34):5063–5069. - 153.
Riley PA. Melanin. Int J Biochem Cell Biol. 1997;29(Ii):1235–1239. - 154.
Siegel SM. Fungal biosorption: A comparative study of metal uptake by penicillium and cladosporil’h. Met Speciat Sep Recover. 1987;1:339. - 155.
Siegel SM, Galun M, Siegel BZ. Filamentous fungi as metal biosorbents: A review. Water Air Soil Pollut. 1990;53(3–4):335–344. - 156.
Rizzo DM, Blanchette RA, Palmer MA. Biosorption of metal ions by Armillaria rhizomorphs . Can J Bot. 1992;70(8):1515–1520. - 157.
Caporalin CB. Comparison of biosorption of rare earth metals by melanized biomass of Aspergillus nidulans fungus in free and immobilized forms [thesis]. Araraquara: Sao Paulo State University, 2011. - 158.
Zhdanova NN, Vasilevskaya AI, Sadovnikov YS, Artyshkova LA. Dynamics of micromycete complexes from soils contaminated with radionuclides. Mikol i Fitopatol. 1990;24(6):504–512. - 159.
Mahmoud YA. Uptake of radionuclides by some fungi. Mycobiology. 2004;32(3):110–114. - 160.
Singleton I, Tobin JM. Fungal interactions with metals and radionuclides for environmental bioremediation. In: Frankland JC, Magan N, Gadd GM, editors. Fungi and Environmental Change. Cambridge: Cambridge University Press; 1996. p. 282–298. - 161.
Steiner M, Linkov I, Yoshida S. The role of fungi in the transfer and cycling of radionuclides in forest ecosystems. J Environ Radioact. 2002;58(2):217–241. - 162.
Zhdanova NN, Tugay T, Dighton J, Zheltonozhsky, V, Mcdermott P. Ionizing radiation attracts soil fungi. Mycol Res. 2004;108(9):1089–1096. - 163.
Dixit R, Wasiullah, Malaviya D, Pandiyan K, Singh UB, Sahu A, et al.. Bioremediation of heavy metals from soil and aquatic environment: An overview of principles and criteria of fundamental processes. Sustain. 2015;7(2):2189–2212. - 164.
Shakya M, Sharma P, Meryem SS, Mahmood Q, Kumar A. Heavy metal removal from industrial wastewater using fungi: Uptake mechanism and biochemical aspects. J Environ Eng. 2015; 142(9):C6015001.