Elsevier

Metabolic Engineering

Volume 31, September 2015, Pages 84-93
Metabolic Engineering

Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli

https://doi.org/10.1016/j.ymben.2015.07.002Get rights and content
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Highlights

  • An artificial novel biosynthetic pathway for fisetin is elucidated.

  • Fisetin is produced in an E. coli cell factory for the first time.

  • This is achieved through expression of nine heterologous genes.

  • Resokaempferol is produced in an E. coli cell factory for the first time.

  • Garbanzol is produced in an E. coli cell factory for the first time.

Abstract

Plant secondary metabolites are an underutilized pool of bioactive molecules for applications in the food, pharma and nutritional industries. One such molecule is fisetin, which is present in many fruits and vegetables and has several potential health benefits, including anti-cancer, anti-viral and anti-aging activity. Moreover, fisetin has recently been shown to prevent Alzheimer׳s disease in mice and to prevent complications associated with diabetes type I. Thus far the biosynthetic pathway of fisetin in plants remains elusive. Here, we present the heterologous assembly of a novel fisetin pathway in Escherichia coli. We propose a novel biosynthetic pathway from the amino acid, tyrosine, utilizing nine heterologous enzymes. The pathway proceeds via the synthesis of two flavanones never produced in microorganisms before – garbanzol and resokaempferol. We show for the first time a functional biosynthetic pathway and establish E. coli as a microbial platform strain for the production of fisetin and related flavonols.

Keywords

Fisetin
Resokaempferol
Garbanzol
Cell factory
Biosynthetic pathway
Polyphenols

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