Synthesis and assembly of fungal melanin

Abstract

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.

Fig. 1

Comparison of DNH (top) and l-dopa (bottom) melanin synthesis pathways. In the DHN pathway, the precursor, malonyl CoA or acetyl CoA, is a substrate of polyketide synthase. Several enzymatic steps are required to produce DHN, the subunit of the melanin polymer. In the l-dopa pathway, the precursor, tyrosine or l-dopa, is a substrate of tyrosinase or laccase. Several enzymatic steps are required to produce dihydroxyindole, the subunit of the melanin polymer

Fig. 2. Model depicting melanin formation in C. neoformans. Laccase containing vesicles are synthesized intracellularly and transported to the cell wall. Here, they interact with melanization substrate such as l-dopa to produce melanin granules. Cell wall polysaccharides such as chitin serve as a scaffold to which the melanin granules are cross-linked