prunetin

7-O-Methyl genistein is a regioselectively methylated derivative of the isoflavonoid genistein, 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 increase metabolic stability and enhance membrane transport, thereby facilitating absorption and improving oral bioavailability and biological activity compared with their unmethylated counterparts [82].

7-O-Methyl genistein exhibits biological activities that include anticancer effects and dose-dependent inhibition of the proliferation of various cancer cell lines, including HepG2 hepatoma, AGS gastric carcinoma, and B16F10 melanoma cells, as well as human umbilical vein endothelial cells. However, 7-O-methylation of genistein has been reported to reduce its antiproliferative and antiangiogenic activities relative to those of the parent compound, genistein [82].

The engineering strategy for its production involves the heterologous expression of a specific O-methyltransferase, such as SaOMT2 from Streptomyces avermitilis, which preferentially utilizes genistein as a substrate. To improve production efficiency, metabolic engineering can be employed to increase the intracellular pool of the essential methyl donor S-adenosyl-L-methionine (SAM) through overexpression of SAM synthase, encoded by metK. Further optimization strategies include the deletion of genes involved in competing methionine and SAM metabolism, such as those encoding SAM decarboxylase and S-adenosyl-L-homocysteine (SAH) hydrolase, to promote intracellular SAM accumulation [82].