Biotransformation-Driven Structural Remodeling of Natural Products by Ganoderma lucidum Fermentation: Mechanisms and Enhanced Bioactivities.

Ganoderma lucidum fermentation (GLF) serves as a sustainable biotransformation platform that precisely modulates the chemical profiles and bioactivities of natural products through enzymatic hydrolysis, microbial metabolic remodeling, and substrate-microbe crosstalk. This review systematically elucidates the GLF-driven structural modifications of key compounds- including polysaccharides, saponins, triterpenoids, flavonoids, and proteins. These structural optimizations synergistically enhance multiple bioactivities: the increased content of deglycosylated ginsenosides enhances antitumor activity, while the antioxidant and prebiotic effects of polysaccharides are potentiated through the regulation of gut microbiota and short-chain fatty acid (SCFA) production. The core mechanisms involve a sophisticated interplay of specific enzyme catalysis, fungal endogenous biosynthesis, and a dynamic "substrate degradation-product synthesis" metabolic cycle. Finally, we emphasize that integrating multi-omics and synthetic biology is crucial for achieving precision control of GLF and advancing its translation in functional foods and drug discovery.