# Fungal Pigments and Their Roles Associated with Human Health
## 2 Types of Fungal Pigments and Their Relevance to Human Health
### Melanin  
Broadly speaking, melanins are heterogeneous polymers derived by the oxidation of phenols and subsequent polymerization of intermediate phenols and their resulting quinones. Fungal melanins are a subset of natural melanins and are polyphenolic and/or polyindolic compounds with high molecular masses and negative charges. Fungal melanins can appear dark green, brown, or black. In fungal cells, melanin serves as an antioxidant and a scavenger of reactive nitrogen species (RNS) and reactive oxygen species (ROS). Commonly found in pathogenic fungi, melanin pigments are thought to provide those pathogens protection from UV and other radiation and aid in evasion from the host's immune system attacks [29]. Fungal melanins belong to three major types: 1,8-dihydroxyoxynaphthalene (DHN) melanin, 3,4-dihydroxyphenylalanine (DOPA)-melanin (also called eumelanin), and pyomelanin [30; 31]. DHN melanin is produced from acetyl-coenzyme A via the polykeletide synthase pathway. The fungus _A. fumigatus_ is able to synthesize DHN melanin, which contributes to the gray-green appearance of its conidia. The deletion of its polykeletide synthase PksP in _A. fumigatus_ gave rise to colorless sporeswith weakened virulence [32]. Eumelanin is converted from \(\omega\)-diphenolic or \(p\)-diphenolic substrates by a polyphenol oxidase (lactcase). In _Candida albicans_, eumelanin particles are observed in vitro and in infected mammalian tissues, such as murine kidney and human skin [33]. In this ascomycete fungus, melanin is externalized in the form of electron-dense melanosomes that are extracellularly secreted or loosely attached to the cell wall surface through binding with chitins [34]. Although _C. albicans_ has lactose activity [33], the association of melanin with pathogenicity remains to be clarified for this fungus. Pyomelanin is an extracellular water-soluble pigment, in contrast to both DHN- and DOPA-melanins that are cell wall-immobilized and insoluble in water [31]. Pyomelanin is produced by the polymerization of homogentisic acid degraded from L-tyrosine/L-phenylalanine. In _A. fumigatus_, pyomelanin plays an important role in the germination of conidia and in the defensive responses toward external oxidative stresses [31].  
Apart from the above-stated three major types of fungal melanians, there is another pathway of melanin biosynthesis in mushrooms such as the common cultivated mushroom _Agaricus bisporus_ and others [35]. In these mushrooms, melanin is formed from a benzoquinone. Benzoquinone is converted from the precursor \(\gamma\)-glutamyl-4-hydroxybenzene (GHB) by tyrosinase. GHB is the main phenolic compound in _A. bisporus_ fruiting bodies and spores [36].  
In addition to its involvement as a virulence factor in fungal pathogens, melanin enables fungi to survive and thrive in adverse and even extreme environments, providing protection against desiccation, non-ionizing (i.e., UV light) and ionizing radiation, as well as oxidative and nitrosative stresses [37; 38]. Over the past decade, melanin pigments and their subunits have kindled great interest as soft biocompatible functional materials with antioxidant characteristics for engineering high-performance, low-impact biocompatible optoelectronic devices, such as light emitting diodes, memory devices, etc. [39]. Intriguingly, halophilic fungal isolates of two species, _Trimmatostroma salinum_ and _Phaeotheca triangularis_, from the eastern coast of the Adriatic Sea, have been found to produce melanin in sodium chloride solutions at saturated concentrations [40]. Similarly, high-dose radiation resistant melanin was found in an Antarctic desert-dwelling (or desert-inhabiting) fungus, _Cryomyces antarcticus_. These fungal extremophiles could serve as promising sources of melanin with excellent physicochemical properties for a variety of industrial and medical applications.