Fungal melanins: Biosynthesis and biological functions

Melanins are hydrophobic polymers of high molecular weight, formed by oxidative polymerization of phenolic and indolic compounds, produced by organisms in all Kingdoms. They are typically black or dark brown in color and their molecular structures are diverse. Several fungi can produce melanins and the functions of this pigment enhance microbial survival under diverse unfavorable environmental and host conditions. The major melanin type encountered among fungi is the 1,8-dihydroxynaphthalene (DHN) melanin that is synthesized from acetyl-coenzyme A via the polyketide pathway. This melanin is generated by several human pathogenic fungi, such as Fonsecaea pedrosoi, Exophialla dermatitidis, Aspergillus fumigatus, Histoplasma capsulatum and Sporothrix schenckii. It is also present in phytopathogenic fungi such as Colletotrichum spp., Magnaporte orizae and Ascochyta rabiei. In addition to DHN melanin, fungi can also produce melanin via dihydroxyphenylalanine (DOPA), in which tyrosinases or laccases hydroxylate tyrosine via DOPA to dopaquinone that then auto-oxidizes and polymerizes, resulting in a polyphenolic heteropolymer of black color known as eumelanin. Cryptococcus neoformans is the best known fungus to produce this type of melanin, but other fungi such as Candida albicans, Paracoccidioides brasiliensis and S. schenckii can also produce eumelanin. A type of soluble fungal melanin is produced from L-tyrosine through p-hydroxyphenylpyruvate and homogentisic acid. This pigment is called pyomelanin and it is similar to alkaptomelanin produced by humans. A. fumigatus, Madurella mycetomatis and Yarrowia lipolytica are examples of fungi that can produce this type of pigment. Fungal melanins play an important role in the protection of fungi from several environmental stresses, such as desiccation, UV irradiation, heavy metals, temperature fluctuation and digestion by hydrolytic enzymes. Melanins also play a role in the virulence of a broad range of pathogenic fungi. These pigments protect the fungi from host defense mechanisms and antifungal agents. Although melanins challenge the immunological strategies of host defense, they are also targets for alternative antimicrobial strategies, by the use of antibodies against melanin or inhibitors of melanin synthesis.