Enzymatic synthesis of a new and bioactive dihydrochalcone: 3,4-dihydroxy-2′,6′-dimethoxy dihydrochalcone

Tyrosinase from <i>Bacillus megaterium</i> (<i>Bm</i>TYR) has been demonstrated to hydroxylate loureirin A and B, compounds found in the ethnomeidicine “dragon’s blood”. Based on the structural similarity, we predicted that <i>Bm</i>TYR also hydroxylate 4-hydroxy-2′,6′-dimethoxy dihydrochalcone (HDDC) and data mining confirmed the novelty of produced compound, 3,4-dihydroxy-2′,6′-dimethoxy dihydrochalcone (DDDC). As predicted, the reaction product analysis showed that <i>Bm</i>TYR biotransformed HDDC into DDDC, with its structure elucidated using mass spectrometry and nucleic magnetic resonance spectroscopy. DDDC exhibited potent free radical scavenging activity, exceeding that of HDDC by more than 100-fold. Second, DDDC showed potent anti-inflammatory activity, which was over 7-fold higher than that of HDDC. Finally, both HDDC and DDDC displayed more than twice the anti-<i>α</i>-glucosidase activity of the clinic drug, acarbose. Moreover, DDDC was more stable in aqueous solution and with less cytotoxicity than HDDC. Overall, DDDC holds great promise as a component in pharmaceutical, cosmetic, and food products.