Functional Amyloid as a Potential Encoder of Melanin Pigments

Melanins are insoluble polymeric pigments that have many important biological functions in diverse life forms. In humans, melanin, which appears in skin, hair, and eyes, is synthesized by melanocytes via oxidative polymerization of tyrosine and additives. Depending upon the location and molecular composition, the melanin can be categorized as black eumelanin (mostly composed of L-dopa), yellow-tored pheomelanin (cysteine as the additive), and neuromelanin (synthesized in the brain), each of which exhibits unique physicochemical properties. As evidenced by their prevalence, melanins have many advantageous features, including broad-range optical absorption and thermal relaxation, permanent radical character, and hydration-dependent electric conductance. Use of melanins or their derivatives to other fields, however, is limited except for surface coating, because unlike other polymers, melanins exhibit heterogeneous and oligomeric molecular structures, extreme insolubility in most solvents, and uncontrollable macroscopic properties. Recently, Lampel et al. suggested a new way to tune the macroscopic properties of melanin-like pigments using selfassembly of tyrosine-containing tripeptides (Figure 1(a)). All possible tripeptides of tyrosine (Y; a residue converted into L-dopa upon enzymatic treatment), phenylalanine (F; an aggregation-prone residue), and aspartic acid (D; a charged residue) formed distinct supramolecular structures with different opacities and solubilities; interestingly, enzymatic oxidation of the structures resulted in pigments with different light absorption, morphology, color, and even electrochemical properties (Figure 1(b) and (c)). For example, DXXand XXD-type peptides (those with paired aromatic residues) formed insoluble hydrogels, while only DXX-type peptides displayed a strong tendency to form dark pigments upon enzymatic oxidation. XDX-type peptides formed neither insoluble supramolecular structures nor strong pigments upon oxidation. The supramolecular orientation of each peptide (before and after oxidation) was investigated with multiple techniques, collectively showing that the differences in pigment properties reflect those in supramolecular order before oxidation. Although a molecular-level understanding of the relationship between the properties of pigments and the intermolecular orientation of the precursors is yet to be completed, the results by Lampel et al. show promise for controlling the properties of melanin pigments by altering not the identity of the assembled molecules, but the way in which they are assembled. This could be projected to a biosynthetic procedure for melanins, which includes the formation of protein fiber matrix as a catalytic scaffold (Figure 2). The intraluminal domain of Pmel17, the major protein component of the matrix, forms amyloid fibrils (non-covalent protein aggregates that are rich in cross-beta sheets) instantaneously under physiological conditions. The currently agreed upon role of Pmel17 matrix is limited to preventing cytotoxic intermediates of melanins to diffuse out of melanosomes (the organelle responsible for melanin synthesis). However, considering that amyloid structures have a highly ordered supramolecular structure, and that the molecular precursors of melanins would likewise be ordered when they penetrate between parallel beta-sheets, Lampel et al.’s results imply that the role of amyloid matrix Figure 1. (a) Schematic illustration of the formation of polymeric peptide pigments by enzymatic oxidation of preorganized tripeptides. (b) Images of self-assembled peptides before (top) and after (bottom) 24 h of enzymatic oxidation. (c) Diverse structures of polymeric peptide pigments. Scale bars: 20, 20, 20, 10 μm. Reprinted with permission. Copyright 2017, AAAS. Highlights DOI: 10.1002/bkcs.11652 N. T. K. Le and K. Kang BULLETIN OF THE KOREAN CHEMICAL SOCIETY