formononetin

7-O-Methyl daidzein is a regioselectively methylated derivative of the isoflavonoid daidzein, in which a methyl group is attached to the 7-hydroxyl group of the A-ring. Methylation of free hydroxyl groups in flavonoids can substantially enhance their metabolic stability and membrane permeability, thereby facilitating absorption and increasing oral bioavailability and, in some cases, biological activity relative to their unmethylated counterparts [82].

7-O-Methyl daidzein exhibits potent inhibitory activity against the growth of various cancer cell lines and effectively suppresses tumor necrosis factor-alpha (TNF-α)-induced invasion of human umbilical vein endothelial cells [82].

The metabolic engineering strategy involves the heterologous expression of a specific O-methyltransferase, such as SaOMT2 from Streptomyces avermitilis, which preferentially utilizes daidzein as a substrate. To achieve high production yields, the intracellular availability of the essential cofactor S-adenosyl-L-methionine (SAM), which serves as the methyl donor for the reaction, can be increased through metabolic engineering approaches, including the overexpression of SAM synthase, encoded by metK [82].