Metabolic engineering of Saccharomyces cerevisiae for de novo production of dihydrochalcones with known antioxidant, antidiabetic, and sweet tasting properties
| Autor: | Ernesto Simon, David Fischer, Christophe Folly, Stefan Martens, Michael Naesby, Beata Joanna Lehka, Michael Eichenberger |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0106 biological sciences
0301 basic medicine Naringenin C4H cinnamate 4-hydroxylase CH3H chalcone 3-hydroxylase F3H flavanone 3β-hydroxylase 01 natural sciences Applied Microbiology and Biotechnology Dihydrochalcones Antioxidants PAL phenylalanine ammonia lyase chemistry.chemical_compound Chalcones Settore BIO/13 - BIOLOGIA APPLICATA OMT O-methyltransferase Original Research Article CHI chalcone isomerase Naringin dihydrochalcone NDC naringin dihydrochalcone biology Chemistry DBR double bond reductase food and beverages HRT homologous recombination tag Dihydrochalcone Nothofagin OD600 optical density at 600 nm Biochemistry Metabolic Engineering CHS chalcone synthase Phlorizin CYP cytochrome P450 Metabolic Networks and Pathways Biotechnology Chalcone synthase Saccharomyces cerevisiae Proteins Phloretin Bioengineering Saccharomyces cerevisiae Double bond reductase DHC dihydrochalcone 03 medical and health sciences VLC very long chain FLS flavonol synthase NHDC neohesperidin dihydrochalcone Hypoglycemic Agents CPR cytochrome P450 reductase UGT UDP-dependent-glycosyltransferase FDA Food and Drug Administration Biosynthetic Pathways 030104 developmental biology Flavonoid biosynthesis Genetic Enhancement F3′H flavonoid 3′-hydroxylase Sweetening Agents EMA European Medicine Agency biology.protein 4CL 4-coumarate-CoA ligase 010606 plant biology & botany STS stilbene synthase |
| Zdroj: | Metabolic Engineering |
| ISSN: | 1096-7176 |
| DOI: | 10.1016/j.ymben.2016.10.019 |
| Popis: | Dihydrochalcones are plant secondary metabolites comprising molecules of significant commercial interest as antioxidants, antidiabetics, or sweeteners. To date, their heterologous biosynthesis in microorganisms has been achieved only by precursor feeding or as minor by-products in strains engineered for flavonoid production. Here, the native ScTSC13 was overexpressed in Saccharomyces cerevisiae to increase its side activity in reducing p-coumaroyl-CoA to p-dihydrocoumaroyl-CoA. De novo production of phloretin, the first committed dihydrochalcone, was achieved by co-expression of additional relevant pathway enzymes. Naringenin, a major by-product of the initial pathway, was practically eliminated by using a chalcone synthase from barley with unexpected substrate specificity. By further extension of the pathway from phloretin with decorating enzymes with known specificities for dihydrochalcones, and by exploiting substrate flexibility of enzymes involved in flavonoid biosynthesis, de novo production of the antioxidant molecule nothofagin, the antidiabetic molecule phlorizin, the sweet molecule naringin dihydrochalcone, and 3-hydroxyphloretin was achieved. Highlights • De novo biosynthesis of phloretin in S. cerevisiae. • De novo pathway extended to various dihydrochalcones of commercial interest. • A barley CHS exhibits very high specificity for phloretin production. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect