Using solid-state NMR to monitor the molecular consequences of cryptococcus neoformans melanization with different catecholamine precursors

Subhasish Chatterjee, Rafael Prados-Rosales, Susana Frases, Boris Itin, Arturo Casadevall, Ruth E. Stark

Research output: Contribution to journalArticle

19 Scopus citations


Melanins are a class of natural pigments associated with a wide range of biological functions, including microbial virulence, energy transduction, and protection against solar radiation. Because of their insolubility and structural heterogeneity, solid-state nuclear magnetic resonance (NMR) spectroscopy provides an unprecedented means to define the molecular architecture of these enigmatic pigments. The requirement of obligatory catecholamines for melanization of the pathogenic fungus Cryptococcus neoformans also offers unique opportunities for investigating melanin development. In the current study, pigments produced with l-dopa, methyl-l-dopa, epinephrine, and norepinephrine precursors are compared structurally using 13C and 1H magic-angle spinning (MAS) NMR. Striking structural differences were observed for both aromatic and aliphatic molecular constituents of the mature fungal pigment assemblies, thus making it possible to redefine the molecular prerequisites for formation of the aromatic domains of insoluble indole-based biopolymers, to rationalize their distinctive physical characteristics, and to delineate the role of cellular constituents in assembly of the melanized macromolecules with polysaccharides and fatty acyl chain-containing moieties. By achieving an augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly, such studies can guide future drug discovery efforts related to melanin-associated virulence, resistance to tumor therapy, and production of melanin mimetics under cell-free conditions.

Original languageEnglish (US)
Pages (from-to)6080-6088
Number of pages9
Issue number31
StatePublished - Aug 7 2012


ASJC Scopus subject areas

  • Biochemistry

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