Sustainable repeated-batch fermentation of immobilized Ganoderma formosanum for enhanced production of anti-melanogenic bioactive compounds

Ganoderma formosanum, an edible medicinal fungus renowned for its bioactive metabolites, faces challenges in traditional cultivation due to prolonged timelines and elevated costs, hindering its integration into functional food formulations. This study introduces an innovative, sustainable fermentation platform by immobilizing G. formosanum mycelia (GFM) on plastic composite support (PCS) within an airlift bioreactor, utilizing agricultural byproducts to foster eco-efficient production of natural anti-melanogenesis compounds with potential as functional food ingredients. Initial shake-flask evaluations identified the SY-PCS matrix, comprising soybean hulls, polypropylene, and yeast extract, as optimal for mycelial immobilization, yielding anti-melanin activity equivalent to 79.78% of kojic acid (KA) efficacy. Upscaling to a 5 L bioreactor with 1% SY-PCS supplementation on day 8 elevated this to 81.7% of KA's potency, while repeated-batch fermentation amplified second-batch biomass productivity by 2.7-fold, promoting resource-efficient yields suitable for food-grade applications. Cell-based assays in B16-F10 models demonstrated potent suppression of intracellular melanin accumulation, akin to KA, and zebrafish trials revealed a 31% reduction in melanin content. LC-MS/MS analysis identified 15 bioactive compounds, corroborated by molecular docking studies showing enhanced tyrosinase-binding affinities and synergistic effects, underscoring their promise as natural additives in functional foods for skin health support.