# Production of Fungal Pigments: Molecular Processes and Their Applications
## 2 Pigmented Fungi and Biosynthesis of Pigments
### Melanins  
Melanins of fungal origin are generated by a complicated polymerization process involving polyketides and free radicals, with the resultant compounds displaying dark green, brown, or black hues. They are resistant to chemical degradation by acids and are insoluble in most solvents; they are only susceptible to degradation by oxidation and are soluble in alkaline solvents [35]. Fungal melanins are negatively charged and hydrophobic [36]. They are deposited in fungal cell walls or as extracellular polymers accumulated in the medium around fungal cells. The production and secretion of melanin is associated with fungal resistance against ultra-violet (UV) irradiation, extreme temperature, enzymatic lysis, oxidants, and desiccation; with maintenance of an appropriate balance of metal ions; and with provision of structural rigidity to cell walls [37]. In other words, melanins represent a kind of fungal adaptation strategy for environmental stresses. On the other hand, in some mammalian pathogenic fungi, exemplified by _Cryptococcus neoformans_, _Apergillus fumigatus, Candida albicans_, _Candida glabrata_, and _Candida parasilosis_, melanins might contribute to fungal virulence, reflecting a resistance mechanism of fungal pathogens to the host immune system, such as macrophages, monocytes, and dendritic cells. Recent investigations have revealed that melanin pigments can lead to antigen masking to circumvent the recognition by host immune system, thereby facilitating the survival of pathogenic fungal species against phagocytosis [6; 38]. Studies with the dematiaceous (darkly-pigmented) fungus _Wangiella dermatitis_, which causes a rare but potentially lethal human mycosis, have shown that loss of melanin production might result in the abolishment of invasive hyphal forms, increased vulnerability to neutrophil killing, and attenuated virulence in the murine infection models [39]. Apart from their protective role and resistance mechanism towards unfavorable conditions, which renders them promising bio-compounds in medicine and the food industry, fungal melanins are also used in the field of material engineering as a novel biopolymer [40]. Of note, two halophilic fungal species, _Trimmatrostroma salinum_ and _Phaeotheca triangularis_, isolated from the eastern coast of the Adriatic Sea, have been reported to produce melanin with a supply of saturated sodium chloride [41]. In addition, an Antarctic desert-inhabiting  
Figure 1: Biosynthesis pathway of \(\beta\)-carotene in _Blakeslea trispora_. This schematic pathway was drawn based on information reviewed in reference [34]. fungus, _Cryomyces antarcticus_, has recently been found to produce melanin pigments possessing high-dose radiation resistance [42]. Collectively, these fungal extremophiles are recognized as prolific sources of melanin with desirable physicochemical properties for industrial and medical applications. Given that both pigmented (melanized) and albino strains of the same fungi can survive and grow under laboratory settings, melanins are not essential for fungal growth (primary metabolism). Rather, they are used for fungal defense and resistance (secondary metabolism) against external conditions, including adverse milieu within host, substantial temperature oscillation, extensive radiation exposure, oxidative stress, osmotic pressure (high salinity), desiccation, and poor nutrient supply. Recent studies have shown that fungi usually synthesize three different kinds of melanin: cell wall immobilized DOPA (dihydroxyphenylalanine)-melanin, DHN (dihydroxynphthalene)-melanin, and extracellular water-soluble pyomelanin [Figure 2]. _A. fumigatus_ is recognized to be able to produce the latter two, whereas _C. neoformans_ can biosynthesize the former one [43]. In _C. neoformans_, DOPA-melanin biosynthesis proceeds through a series of oxidation-reduction reactions, starting from tyrosine or L-3\(A\) dihydroxyphenylalanine (L-dopa) (see Figure 2a for details).