Glycosylation and methylation in the biosynthesis of isoflavonoids in Pueraria lobata

Abstract

The pathway for forming isoflavonoid skeletal structure is primarily restricted to the Leguminosae family. Subsequent decorations on the compound backbone by tailoring enzymes would change their biological and medicinal properties. Pueraria lobata is a leguminous plant, and as a traditional Chinese medicine its roots have been ascribed a number of pharmacological activities. Glycosylation and methylation are the main modifying processes in isoflavonoid metabolism in P. lobata roots, resulting in the accumulation of unique glycosylated and methylated end isoflavonoid compounds. For instance, daidzein 8-C-glucoside (i.e., puerarin) and puerarin derivatives are produced only by the Pueraria genus. Puerarin has been established as a clinical drug for curing cardiovascular diseases. To better understand the characteristic isoflavonoid metabolism in P. lobata, this review attempts to summarize the research progress made with understanding the main glycosylation and methylation of isoflavonoids in P. lobata and their biosynthetic enzymes.

Keywords: biosynthesis; glycosylation; isoflavonoid; methylation; pueraria.

Figure 1

The medicinal plant Pueraria lobata and the main glycosylated and methylated isoflavonoids accumulated in it. (A) P. lobata plant. (B) The dried roots of P. lobata used in traditional Chinese medicine. (C) Structures of the main isoflavone glucosides. (D) Structures of the main O-methylated isoflavonoids.

Figure 2

Proposed biosynthesis in P. lobata of the main glycosylated and methylated isoflavonoids based on the properties of the P. lobata UGTs and OMTs characterized so far. PAL, phenylalanine ammonialyase; C4H, cinnamate 4-hydroxylase; 4CL, 4-coumarate CoA ligase; CHS, chalcone synthase; CHR, chalcone reductase; CHI, chalcone isomerase; 2-HIS, 2-hydroxyisoflavanone synthase; 2-HID, 2-hydroxyisoflavanone dehydratase; UGT, UDP-glucosyltransferase; OMT, O-methyltransferase.