Toward developing a yeast cell factory for the production of prenylated flavonoids

Mark Levisson, Carla Araya-Cloutier, Wouter J.C. De Bruijn, Menno Van Der Heide, José Manuel Salvador López, Jean Marc Daran, Jean Paul Vincken, Jules Beekwilder

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

Abstract

Prenylated flavonoids possess a wide variety of biological activities, including estrogenic, antioxidant, antimicrobial, and anticancer activities. Hence, they have potential applications in food products, medicines, or supplements with health-promoting activities. However, the low abundance of prenylated flavonoids in nature is limiting their exploitation. Therefore, we investigated the prospect of producing prenylated flavonoids in the yeast Saccharomyces cerevisiae. As a proof of concept, we focused on the production of the potent phytoestrogen 8-prenylnaringenin. Introduction of the flavonoid prenyltransferase SfFPT from Sophora flavescens in naringenin-producing yeast strains resulted in de novo production of 8-prenylnaringenin. We generated several strains with increased production of the intermediate precursor naringenin, which finally resulted in a production of 0.12 mg L -1 (0.35 μM) 8-prenylnaringenin under shake flask conditions. A number of bottlenecks in prenylated flavonoid production were identified and are discussed.

Original languageEnglish
JournalJournal of Agricultural and Food Chemistry
DOIs
Publication statusE-pub ahead of print - 24 Apr 2019

Fingerprint

factories
Flavonoids
Yeast
Industrial plants
flavonoids
Yeasts
Cells
yeasts
naringenin
cells
Dimethylallyltranstransferase
Sophora flavescens
Sophora
Phytoestrogens
health promotion
plant estrogens
Bioelectric potentials
Bioactivity
Medicine
Saccharomyces cerevisiae

Keywords

  • 8-prenylnaringenin
  • de novo
  • metabolic engineering
  • naringenin
  • prenylated flavonoids
  • Saccharomyces cerevisiae

Cite this

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title = "Toward developing a yeast cell factory for the production of prenylated flavonoids",
abstract = "Prenylated flavonoids possess a wide variety of biological activities, including estrogenic, antioxidant, antimicrobial, and anticancer activities. Hence, they have potential applications in food products, medicines, or supplements with health-promoting activities. However, the low abundance of prenylated flavonoids in nature is limiting their exploitation. Therefore, we investigated the prospect of producing prenylated flavonoids in the yeast Saccharomyces cerevisiae. As a proof of concept, we focused on the production of the potent phytoestrogen 8-prenylnaringenin. Introduction of the flavonoid prenyltransferase SfFPT from Sophora flavescens in naringenin-producing yeast strains resulted in de novo production of 8-prenylnaringenin. We generated several strains with increased production of the intermediate precursor naringenin, which finally resulted in a production of 0.12 mg L -1 (0.35 μM) 8-prenylnaringenin under shake flask conditions. A number of bottlenecks in prenylated flavonoid production were identified and are discussed.",
keywords = "8-prenylnaringenin, de novo, metabolic engineering, naringenin, prenylated flavonoids, Saccharomyces cerevisiae",
author = "Mark Levisson and Carla Araya-Cloutier and {De Bruijn}, {Wouter J.C.} and {Van Der Heide}, Menno and {Salvador L{\'o}pez}, {Jos{\'e} Manuel} and Daran, {Jean Marc} and Vincken, {Jean Paul} and Jules Beekwilder",
year = "2019",
month = "4",
day = "24",
doi = "10.1021/acs.jafc.9b01367",
language = "English",
journal = "Journal of Agricultural and Food Chemistry",
issn = "0021-8561",
publisher = "American Chemical Society",

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Toward developing a yeast cell factory for the production of prenylated flavonoids. / Levisson, Mark; Araya-Cloutier, Carla; De Bruijn, Wouter J.C.; Van Der Heide, Menno; Salvador López, José Manuel; Daran, Jean Marc; Vincken, Jean Paul; Beekwilder, Jules.

In: Journal of Agricultural and Food Chemistry, 24.04.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Toward developing a yeast cell factory for the production of prenylated flavonoids

AU - Levisson, Mark

AU - Araya-Cloutier, Carla

AU - De Bruijn, Wouter J.C.

AU - Van Der Heide, Menno

AU - Salvador López, José Manuel

AU - Daran, Jean Marc

AU - Vincken, Jean Paul

AU - Beekwilder, Jules

PY - 2019/4/24

Y1 - 2019/4/24

N2 - Prenylated flavonoids possess a wide variety of biological activities, including estrogenic, antioxidant, antimicrobial, and anticancer activities. Hence, they have potential applications in food products, medicines, or supplements with health-promoting activities. However, the low abundance of prenylated flavonoids in nature is limiting their exploitation. Therefore, we investigated the prospect of producing prenylated flavonoids in the yeast Saccharomyces cerevisiae. As a proof of concept, we focused on the production of the potent phytoestrogen 8-prenylnaringenin. Introduction of the flavonoid prenyltransferase SfFPT from Sophora flavescens in naringenin-producing yeast strains resulted in de novo production of 8-prenylnaringenin. We generated several strains with increased production of the intermediate precursor naringenin, which finally resulted in a production of 0.12 mg L -1 (0.35 μM) 8-prenylnaringenin under shake flask conditions. A number of bottlenecks in prenylated flavonoid production were identified and are discussed.

AB - Prenylated flavonoids possess a wide variety of biological activities, including estrogenic, antioxidant, antimicrobial, and anticancer activities. Hence, they have potential applications in food products, medicines, or supplements with health-promoting activities. However, the low abundance of prenylated flavonoids in nature is limiting their exploitation. Therefore, we investigated the prospect of producing prenylated flavonoids in the yeast Saccharomyces cerevisiae. As a proof of concept, we focused on the production of the potent phytoestrogen 8-prenylnaringenin. Introduction of the flavonoid prenyltransferase SfFPT from Sophora flavescens in naringenin-producing yeast strains resulted in de novo production of 8-prenylnaringenin. We generated several strains with increased production of the intermediate precursor naringenin, which finally resulted in a production of 0.12 mg L -1 (0.35 μM) 8-prenylnaringenin under shake flask conditions. A number of bottlenecks in prenylated flavonoid production were identified and are discussed.

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KW - Saccharomyces cerevisiae

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M3 - Article

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