Metabolic engineering of Escherichia coli for the production of silybin

Abstract

Silybin, a kind of flavonolignan, is the most active compound in silymarin, extracts from milk thistle. Silybin has various pharmacological effects, such as anti-hepatotoxic, anti-inflammatory, anti-cancer, anti-oxidant, antimicrobial, and antibacterial activities. Silybin is widely used as medicine, and healthcare products. However, silybin is generated extremely low by the herbal source. Furthermore, the supply of silybin depends solely on the seed extraction of milk thistle, which is unstable, toxic, and inefficient. Thus, an efficient, and eco-compatible method for the production of silybin is required. In this study, we suggest novel synthesis of silybin using Escherichia coli as a platform strain. First, E. coli strains were engineered to produce silybin precursors, coniferyl alcohol, and dihydroquercetin. By introducing plant phenylpropanoid biosynthetic pathway into E. coli, coniferyl alcohol was produced. By introducing plant flavonoid biosynthetic pathway into E. coli, dihydroquercetin was produced. Since there are no enzyme available for the reaction of combining coniferyl alcohol, and dihydroquercetin, silybin was synthesized from the two precursors by chemical reaction. This result demonstrated that silybin can be produced by the chemical reaction of coniferyl alcohol, and dihydroquercetin produced from the recombinant E. coli strains. In this study, it was exhibited that the heterologous production of silybin may be achieved from simple carbon source, such as glucose, or glycerol using microorganisms.