Biosynthesis of dihydroquercetin in Escherichia coli from glycerol

Phenylpropanoids are a group of diverse natural products derived from aromatic amino acids. Although their demands are high both as drugs and nutraceuticals, their production mainly depends on inefficient extraction from plants. To achieve sustainable production of phenylpropanoids, engineering model microorganisms such as Escherichia coli has been sought, but most strains require supplementation of expensive precursors. Here, we report one-step production of a representative phenylpropanoid, dihydroquercetin (DHQ), from simple carbon sources in E. coli for the first time. The best DHQ producer strain capable of producing 239.4 mg/L of DHQ from glycerol was obtained by optimizing the biosynthetic pathway and engineering the signal peptide of cytochrome P450 (TT7) from Arabidopsis thaliana. The engineered plant P450 could produce a significantly higher titer of DHQ than a bacterial monooxygenase, showing the potential of employing plant P450s for the production of diverse natural products that has been previously difficult in bacterial hosts. This study will serve as a guideline for industrial production of pharmaceutically important yet complex natural products.