Prenylation of flavonoids by DMATS1 and their anti-inflammatory activities

Prenylated flavonoids are widely distributed in plants, including fruits and vegetables in the Moraceae and Fabaceae families. These chemicals are potential functional food ingredients owing to their attractive biological activities. However, natural prenylated flavonoids are rare, which limits their application.

Here, we reported the prenylation of apigenin and genistein catalyzed by DMATS1, a dimethylallyl-l-tryptophan synthase from Fusarium fujikuroi. High-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance identified their structure as 6-C-prenylapigenin (6-PA) and 6-C-prenylgenistein (6-PG), respectively. Cell-based assay suggested that both 6-PA and 6-PG induced the proliferation of THP-1 cells under low concentrations and were safe in doses less than 50 μmol L^-1. 6-PA and 6-PG exhibited significant anti-inflammatory activity in lipopolysaccharide-stimulated THP-1 cells, and inhibited the production of nitric oxide as well as downregulating the transcriptional levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-8, and interleukin-1β.

The findings suggested that DMATS1 could catalyze the 6-C prenylation of apigenin and genistein, and the generated 6-PA and 6-PG exhibited anti-inflammatory activity, aiding in the recognition of 6-PA and 6-PG as nutraceuticals. © 2025 Society of Chemical Industry.