Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA

Helene C. Eisenman, Mascha Mues, Sarah E. Weber, Susana Frases, Stuart Chaskes, Gary J. Gerfen, Arturo Casadevall

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The human fungal pathogen Cryptococcus neoformans produces melanin in the presence of various substrates, including the L enantiomer of 3,4-dihydroxyphenylalanine (DOPA). The enzyme laccase catalyses the formation of melanin by oxidizing L-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 C. neoformans to produce pigments from a variety of available substrates is likely to confer a survival advantage. A number of C. neoformans isolates of different serotypes produced pigments from D-DOPA, the stereoisomer of L-DOPA. Acid-resistant particles were isolated from pigmented C. neoformans cells grown in the presence of D-DOPA. Biophysical characterization showed the particles had a stably detectable free-radical signal by EPR, and negative zeta potential, similar to L-DOPA-derived particles. No major differences were found between L- and D-DOPA ghosts in terms of binding to anti-melanin antibodies, or in overall architecture when imaged by electron microscopy. C. neoformans cells utilized L- and D-DOPA at a similar rate. Overall, our results indicate that C. neoformans shows little stereoselectivity for utilizing DOPA in melanin synthesis. The ability of C. neoformans to use both L and D 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.

Original languageEnglish (US)
Pages (from-to)3954-3962
Number of pages9
JournalMicrobiology
Volume153
Issue number12
DOIs
StatePublished - Dec 2007

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Laccase
Dihydroxyphenylalanine
Cryptococcus neoformans
Melanins
Stereoisomerism
Levodopa
Polymerization
Cell Wall
Free Radicals
Anti-Idiotypic Antibodies
Electron Microscopy
Yeasts
Acids
Survival
Enzymes

ASJC Scopus subject areas

  • Microbiology

Cite this

Eisenman, H. C., Mues, M., Weber, S. E., Frases, S., Chaskes, S., Gerfen, G. J., & Casadevall, A. (2007). Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA. Microbiology, 153(12), 3954-3962. https://doi.org/10.1099/mic.0.2007/011049-0

Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA. / Eisenman, Helene C.; Mues, Mascha; Weber, Sarah E.; Frases, Susana; Chaskes, Stuart; Gerfen, Gary J.; Casadevall, Arturo.

In: Microbiology, Vol. 153, No. 12, 12.2007, p. 3954-3962.

Research output: Contribution to journalArticle

Eisenman, HC, Mues, M, Weber, SE, Frases, S, Chaskes, S, Gerfen, GJ & Casadevall, A 2007, 'Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA', Microbiology, vol. 153, no. 12, pp. 3954-3962. https://doi.org/10.1099/mic.0.2007/011049-0
Eisenman, Helene C. ; Mues, Mascha ; Weber, Sarah E. ; Frases, Susana ; Chaskes, Stuart ; Gerfen, Gary J. ; Casadevall, Arturo. / Cryptococcus neoformans laccase catalyses melanin synthesis from both D- and L-DOPA. In: Microbiology. 2007 ; Vol. 153, No. 12. pp. 3954-3962.
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