Production of Four Flavonoid C -Glucosides in Escherichia coli

Flavonoid C -glucosides, which are found in several plant families, are characterized by several biological properties, including antioxidant, anticancer, anti-inflammatory, neuroprotective, hepatoprotective, cardioprotective, antibacterial, antihyperalgesic, antiviral, and antinociceptive activities. The biosynthetic pathway of flavonoid C -glucosides in plants has been elucidated. In the present study, a pathway was introduced to Escherichia coli to synthesize four flavonoid C -glucosides, namely, isovitexin, vitexin, kaempferol 6- C -glucoside, and kaempferol 8- C -glucoside. A five- or six-step metabolic pathway for synthesizing flavonoid aglycones from tyrosine was constructed and two regioselective flavonoid C -glycosyltransferases from Wasabia japonica ( WjGT1 ) and Trollius chinensis ( TcCGT ) were used. Additionally, the best shikimate gene module construct was selected to maximize the titer of each C- glucoside flavonoid. Isovitexin (30.2 mg/L), vitexin (93.9 mg/L), kaempferol 6- C -glucoside (14.4 mg/L), and kaempferol 8- C -glucoside (38.6 mg/L) were synthesized using these approaches. The flavonoid C -glucosides synthesized in this study provide a basis for investigating and unraveling their novel biological properties.