Luteolin (Lut) and apigenin (Apn), flavones present in various edible plants, exhibit diverse antioxidant and pharmacological activities but have limited in vivo efficacy due to low water solubility and poor bioavailability. Here, we generated luteolin and apigenin monophosphate derivatives (LutPs and ApnPs) individually via microbial biotransformation. We then characterized their physicochemical properties and evaluated their in vitro and in vivo pharmacokinetics and bioavailability. Both LutPs and ApnPs showed enhanced solubility and dissolution and remained stable in simulated gastrointestinal conditions. Additionally, they efficiently reverted to parental forms via alkaline phosphatase in Caco-2 cells. Following oral administration in rats, LutPs and ApnPs exhibited higher plasma exposure to both aglycone and conjugated forms compared to Lut and Apn. Notably, the in vivo biotransformation of Apn to Lut was observed in all apigenin-related groups. Our study suggests that flavone monophosphates are effective alternatives with enhanced bioavailability, providing insights for the potential application of emerging bioactive nutraceuticals.

Ganoderic acids (GAs) are bioactive lanostane-type triterpenoids produced by Ganoderma lucidum that accumulate predominantly in fruiting bodies, whose long cultivation period limits their practical production. Using Global Natural Products Social Molecular Networking (GNPS), we identified G. lucidum TM701, which accumulated 99 GA derivatives in mycelia and exhibited higher triterpenoid levels and greater chemical diversity than the commercial strain BCRC 36203. Four abundant GAs (GA-Mb/Mc, GA-S/Mf, GA-T, and GA-R) were selected as marker compounds for monitoring GA production. A modified two-stage cultivation strategy, combining submerged inoculum preparation with nutrient optimization during static cultivation, increased GA production to 1396 mg L⁻¹ GAs in potato dextrose broth supplemented with 2% glucose. Heat treatment revealed interconversion among GA-Mb/Mc, GA-Mh, and GA-P/Q, indicating a dehydration-driven stabilization of conjugated diene structures. G. lucidum TM701 mycelia not only provide a platform for triterpenoid production, but also serve as a promising model for elucidating GA biosynthesis and investigating their thermal transformation.