Fungal melanin as a bioactive biopolymer: structural diversity, oxidative stress modulation, anticancer mechanisms, and therapeutic perspectives

Fungal melanin is a multifunctional biopolymer platform with significant potential in oxidative stress modulation and cancer therapy. This review presents an integrated structure-property-activity framework to examine how biosynthetic pathways, precursor chemistry, functional group composition, oxidation state, molecular/particle characteristics, and extraction procedures influence the biological performance of fungal melanins. Key biosynthetic routes, including DOPA-eumelanin, DOPA-pheomelanin, DHN-melanin, pyomelanin, and minor pathways, are detailed alongside recent developments in extraction and purification technologies. The review critically evaluates the chemical and cellular mechanisms underlying free radical scavenging, electron transfer, redox buffering, metal-ion chelation, mitochondrial protection, and redox-sensitive signaling pathway regulation. Furthermore, it addresses the context-dependent interplay between antioxidant and anticancer activities, distinguishing established experimental findings from proposed mechanisms. Applications in photothermal therapy, drug delivery, combination approaches, and immunomodulation are highlighted. By addressing key experimental variables, research gaps, and translational challenges, this review provides crucial insights for standardizing fungal melanin production and advancing its clinical development.