TY - JOUR
T1 - The melanization road more traveled by
T2 - Precursor substrate effects on melanin synthesis in cell-free and fungal cell systems
AU - Chatterjee, Subhasish
AU - Prados-Rosales, Rafael
AU - Tan, Sindy
AU - Phan, Van Chanh
AU - Chrissian, Christine
AU - Itin, Boris
AU - Wang, Hsin
AU - Khajo, Abdelahad
AU - Magliozzo, Richard S.
AU - Casadevall, Arturo
AU - Stark, Ruth E.
N1 - Publisher Copyright:
© 2018 Chatterjee et al.
PY - 2018/12/28
Y1 - 2018/12/28
N2 - Natural brown– black eumelanin pigments confer structural coloration in animals and potently block ionizing radiation and antifungal drugs. These functions also make them attractive for bioinspired materials design, including coating materials for drug-delivery vehicles, strengthening agents for adhesive hydrogel materials, and free-radical scavengers for soil remediation. Nonetheless, the molecular determinants of the melanin “developmental road traveled” and the resulting architectural features have remained uncertain because of the insoluble, heterogeneous, and amorphous characteristics of these complex polymeric assemblies. Here, we used 2D solid-state NMR, EPR, and dynamic nuclear polarization spectroscopic techniques, assisted in some instances by the use of isotopically enriched precursors, to address several open questions regarding the molecular structures and associated functions of eumelanin. Our findings uncovered: 1) that the identity of the available catecholamine precursor alters the structure of melanin pigments produced either in Cryptococcus neoformans fungal cells or under cell-free conditions; 2) that the identity of the available precursor alters the scaffold organization and membrane lipid content of melanized fungal cells; 3) that the fungal cells are melanized preferentially by an L-DOPA precursor; and 4) that the macromolecular carbon- and nitrogen-based architecture of cell-free and fungal eumelanins includes indole, pyrrole, indolequinone, and open-chain building blocks that develop depending on reaction time. In conclusion, the availability of catecholamine precursors plays an important role in eumelanin development by affecting the efficacy of pigment formation, the melanin molecular structure, and its underlying scaffold in fungal systems.
AB - Natural brown– black eumelanin pigments confer structural coloration in animals and potently block ionizing radiation and antifungal drugs. These functions also make them attractive for bioinspired materials design, including coating materials for drug-delivery vehicles, strengthening agents for adhesive hydrogel materials, and free-radical scavengers for soil remediation. Nonetheless, the molecular determinants of the melanin “developmental road traveled” and the resulting architectural features have remained uncertain because of the insoluble, heterogeneous, and amorphous characteristics of these complex polymeric assemblies. Here, we used 2D solid-state NMR, EPR, and dynamic nuclear polarization spectroscopic techniques, assisted in some instances by the use of isotopically enriched precursors, to address several open questions regarding the molecular structures and associated functions of eumelanin. Our findings uncovered: 1) that the identity of the available catecholamine precursor alters the structure of melanin pigments produced either in Cryptococcus neoformans fungal cells or under cell-free conditions; 2) that the identity of the available precursor alters the scaffold organization and membrane lipid content of melanized fungal cells; 3) that the fungal cells are melanized preferentially by an L-DOPA precursor; and 4) that the macromolecular carbon- and nitrogen-based architecture of cell-free and fungal eumelanins includes indole, pyrrole, indolequinone, and open-chain building blocks that develop depending on reaction time. In conclusion, the availability of catecholamine precursors plays an important role in eumelanin development by affecting the efficacy of pigment formation, the melanin molecular structure, and its underlying scaffold in fungal systems.
UR - http://www.scopus.com/inward/record.url?scp=85059229639&partnerID=8YFLogxK
U2 - 10.1074/jbc.RA118.005791
DO - 10.1074/jbc.RA118.005791
M3 - Article
C2 - 30385508
AN - SCOPUS:85059229639
SN - 0021-9258
VL - 293
SP - 20157
EP - 20168
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -