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

Steen Gustav Stahlhut, Solvej Siedler, Sailesh Malla, Scott James Harrison, Jerome Maury, Ana Rute Neves, Jochen Förster

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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.
Original languageEnglish
JournalMetabolic Engineering
Volume31
Pages (from-to)84-93
Number of pages10
ISSN1096-7176
DOIs
Publication statusPublished - 2015

Bibliographical note

This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

Keywords

  • Fisetin
  • Resokaempferol
  • Garbanzol
  • Cell factory
  • Biosynthetic pathway
  • Polyphenols

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