1887

Abstract

The human fungal pathogen produces melanin in the presence of various substrates, including the enantiomer of 3,4-dihydroxyphenylalanine (DOPA). The enzyme laccase catalyses the formation of melanin by oxidizing -DOPA, initiating a series of presumably spontaneous reactions that ultimately leads to the polymerization of the pigment in the yeast cell wall. There, melanin protects the cell from a multitude of environmental and host assaults. Thus, the ability of to produce pigments from a variety of available substrates is likely to confer a survival advantage. A number of isolates of different serotypes produced pigments from -DOPA, the stereoisomer of -DOPA. Acid-resistant particles were isolated from pigmented cells grown in the presence of -DOPA. Biophysical characterization showed the particles had a stably detectable free-radical signal by EPR, and negative zeta potential, similar to -DOPA-derived particles. No major differences were found between - and -DOPA ghosts in terms of binding to anti-melanin antibodies, or in overall architecture when imaged by electron microscopy. cells utilized - and -DOPA at a similar rate. Overall, our results indicate that shows little stereoselectivity for utilizing DOPA in melanin synthesis. The ability of to use both and enantiomers for melanization implies that this organism has access to a greater potential pool of substrates for melanin synthesis, and this could potentially be exploited in the design of therapeutic inhibitors of laccase.

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2007-12-01
2019-10-23
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