Biotransformation of dihydrocapsaicin by human intestinal fungi and the inhibitory effects of metabolites against LSD1.

Dihydrocapsaicin is the main bioactive component in plants, which is widely used in China and India as a food drug and additive. In this study, the biotransformation of dihydrocapsaicin was performed using four cultivated human intestinal fungal strains . Eight metabolites, including seven previously undescribed metabolites ( and -) and one known analog (), were obtained. Numerous spectroscopic data, such as NMR and HRESIMS, were collected to determine their structures. Based on the structures of the dihydrocapsaicin metabolites, the main biotransformation reactions were revealed to be hydroxylation, alcohol oxidation, and lactylation. In particular, the lactylation of hydroxyl groups is mainly mediated by R2701. In addition, metabolite showed significant inhibitory effect on lysine-specific demethylase 1 (LSD1) (IC 1.99 μM). Therefore, the biotransformation of dihydrocapsaicin by intestinal fungi afforded various derivatives, which were important resources for developing LSD1 inhibitors and potential application in cancer treatment.