title: Assembly of a novel biosynthetic pathway for production of the plant flavonoid fisetin in Escherichia coli.
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.
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Steen G
authors.initials: SG
authors.lastname: Stahlhut
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Solvej
authors.initials: S
authors.lastname: Siedler
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Sailesh
authors.initials: S
authors.lastname: Malla
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Harrison
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Maury
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark.
authors.forename: Ana Rute
authors.initials: AR
authors.lastname: Neves
authors.affiliation: Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Allé 6, 2970 Hørsholm, Denmark. Electronic address: jfor@biosustain.dtu.dk.
authors.forename: Jochen
authors.initials: J
authors.lastname: Forster
mesh_terms: D004926:Escherichia coli / Q000378:metabolism*; D044950:Flavanones / Q000096:biosynthesis; D005419:Flavonoids / Q000096:biosynthesis* / Q000737:chemistry; D044948:Flavonols; D014443:Tyrosine / Q000378:metabolism
chemical_list: D044950:Flavanones; D005419:Flavonoids; D044948:Flavonols; D014443:Tyrosine; C017875:fisetin; C083152:liquiritigenin
keywords: Biosynthetic pathway; Cell factory; Fisetin; Garbanzol; Polyphenols; Resokaempferol