Biotransformation of Flavonoids Improves Antimicrobial and Anti-Breast Cancer Activities In Vitro.

Coarse cereals are rich in flavonoids, which are bioactive substances with a wide range of functions. Biotransformation is considered an emerging approach to methylate flavonoids, displaying prominent regio- and stereoselectivity. In the current study, liquiritigenin, naringenin, and hesperidin flavonoids were biotransformed using O-methyltransferases that were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA. Nuclear magnetic resonance (NMR) spectroscopy was used together with high-resolution mass spectroscopy analysis to determine the structures of the resulting methylated transformants, and their antimicrobial and antiproliferation activities were also characterized. Among the five methylated flavonoids obtained, 7-methoxy-liquiritigenin had the strongest inhibitory effect on Candida albicans SC5314 (C. albicans SC5314), Staphylococcus aureus ATCC6538 (S. aureus ATCC6538), and Escherichia coli ATCC25922 (E. coli ATCC25922), which increased 7.65-, 1.49-, and 0.54-fold in comparison to the values of their unmethylated counterparts at 200, 250, and 400 µM, respectively. The results suggest that 3'-methoxyhesperetin showed the best antiproliferative activity against MCF-7 cells with IC50 values of 10.45 ± 0.45 µM, which was an increase of more than 14.35-fold compared to that of hesperetin. These results indicate that methylation enhances the antimicrobial activities and antiproliferative effects of flavonoids. The current study provides an experimental basis for further research on flavonoids as well as flavonoid-containing crops in the development of antimicrobial and anti-breast cancer drugs in addition to supplementary and health foods. The biotransformation method is ideal, as it represents a means for the sustainable production of bioactive flavonoids.