Fungal Polysaccharides as Next-Generation Bioactive: Advances in Structure–Activity Mapping, Mode of Action, and Biotechnological Horizons

Abstract

Fungal polysaccharides (FPs) represent a diverse class of bioactive macromolecules widely studied for their nutritional, therapeutic, and biotechnological value. This review synthesizes recent advances (2020–2025) in the structural characterization, biological functions, and translational potential of FPs. Findings show that monosaccharide composition (MC), molecular weight (Mw), glycosidic linkage patterns, and higher order conformations, particularly β-(1→3)/(1→6) triple-helical structures, are the primary determinants of bioactivity. Structure–activity evidence indicates that glucose-rich β-glucans enhance immunomodulation and antitumor responses, while mannose and rhamnose-enriched heteropolysaccharides contribute to hypoglycemic and antioxidant effects. Molecular studies further reveal that FPs regulate multiple signaling pathways, including TLR4/NF-κB, MAPK, PI3K/Akt, and Nrf2, thereby mediating immune activation, inflammation suppression, oxidative stress reduction, and metabolic homeostasis. Across biological activities, FPs demonstrate strong immunoregulatory, antitumor, antioxidant, hypoglycemic, hepatoprotective, and lipid-modulating effects, with growing evidence of microbiota-dependent mechanisms and synergy with conventional therapies. This review highlights that specific structural motifs and conformational attributes are directly linked to functional performance, providing a foundation for predictable structure–activity models. We conclude that FPs hold significant promise as next-generation functional ingredients, therapeutic adjuvants, and biomaterial platforms. However, their translation requires standardized analytical methods, deeper mechanistic studies, and well-designed clinical investigations.