Toward developing a yeast cell factory for the production of prenylated flavonoids
Mark Levisson (Wageningen University & Research)
Carla Araya-Cloutier (Wageningen University & Research)
Wouter J.C. De Bruijn (Wageningen University & Research)
Menno Van Der Heide (Wageningen University & Research)
José Manuel Salvador López (Wageningen University & Research)
Jean Marc G Daran (TU Delft - BT/Industriele Microbiologie)
Jean Paul Vincken (Wageningen University & Research)
Jules Beekwilder (Wageningen University & Research)
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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.
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