Flavonoids are ubiquitous plant secondary metabolites that are consumed by humans through a wide variety of dietary sources, including fruits, vegetables, and tea. Flavonoids exhibit many interesting biological effects in both in vitro and in vivo studies that suggest their potential therapeutic value for prevention of diseases such as cancer and neurodegeneration. While the so-called antioxidant activity of flavonoids are frequently cited as a mechanistic explanation for their varied bioactivities, very little direct evidence supports this hypothesis. Instead, flavonoids probably induce biological effects through the formation of covalent adducts with proteins. In this study, we use the enzyme enoyl-ACP reductase from Escherichia coli as a model system to explore the mechanisms of flavonoid inhibition of this important bacterial enzyme. The flavonoid quercetin exhibited low micromolar inhibitory activity against this enzyme. Peroxide production assays demonstrated that quercetin did not generate significant quantities of peroxides in the aqueous buffer used in the enzyme assays; assays using microcentrifugation filters were also performed for quercetin to determine the reversibility of its inhibitory activity. The flavonoids (+)-catechin and rutin were also evaluated but they exhibited no inhibitory activity against the enzyme despite their structural similarity to quercetin. The results show that the so-called antioxidant activity of flavonoids cannot explain their inhibitory activity against enoyl-ACP reductase. The results also suggest that quercetin may inhibit enoyl-ACP reductase via a unique mechanism and further exploration of this mechanism could reveal new strategies for the development of antibacterial drugs.

Mechanistic investigation of flavonoid inhibitors of the bacterial fatty acid synthase enzyme enyol-ACP reductase

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.