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.

Phenolic C-glycoside synthesis using microbial systems.

Plants produce different types of phenolic compounds. The majority of these compounds are glycosylated. Phenolic O-glycosides are also common. Recently, C-glycosylation of phenolic compounds has received attention because of the biological importance of phenolic C-glycosides. To date, three classes of C-glycosyltransferases (CGTs) have been characterized based on the type of sugar acceptor: flavonoid CGT, coumarin CGT, and xanthone CGT. Phylogenetic analysis of glycosyltransferases has revealed that CGTs form a distinct class that is clearly different from that of O-glycosyltransferases. The characterized CGTs have been introduced into microbial systems to synthesize phenolic C-glycosides. Here, we review recent progress in the development of CGTs and their application in the synthesis of phenolic C-glycosides using microbial systems.