Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae 

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Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae . / Garcia Vanegas, Katherina; Larsen, Arésu Bondrup; Eichenberger, Michael; Fischer, David; Mortensen, Uffe Hasbro; Naesby, Michael.

In: Microbial Cell Factories, Vol. 17, 107, 2018.

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

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Garcia Vanegas, Katherina ; Larsen, Arésu Bondrup ; Eichenberger, Michael ; Fischer, David ; Mortensen, Uffe Hasbro ; Naesby, Michael. / Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae . In: Microbial Cell Factories. 2018 ; Vol. 17.

Bibtex

@article{a2bc3df1be1f4d0cba16422a8a4e4815,
title = "Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae ",
abstract = "Background: C-glycosylated flavones have recently attracted increased attention due to their possible benefits in human health. These biologically active compounds are part of the human diet, and the C-linkage makes them more resistant to hydrolysis and degradation than O-glycosides. In contrast to O-glycosyltransferases, few C-glycosyltransferases (CGTs) have so far been characterized. Two different biosynthetic routes for C-glycosylated flavones have been identified in plants. Depending on the type of C-glycosyltransferase, flavones can be glycosylated either directly or indirectly via C-glycosylation of a 2-hydroxyflavanone intermediate formed by a flavanone 2-hydroxylase (F2H).Results: In this study, we reconstructed the pathways in the yeast Saccharomyces cerevisiae, to produce some relevant CGT substrates, either the flavanones naringenin and eriodictyol or the flavones apigenin and luteolin. We then demonstrated two-step indirect glycosylation using combinations of F2H and CGT, to convert 2-hydroxyflavanone intermediates into the 6C-glucoside flavones isovitexin and isoorientin, and the 8C-glucoside flavones vitexin and orientin. Furthermore, we established direct glycosylation of flavones using the recently identified GtUF6CGT1 from Gentiana triflora. The ratio between 6C and 8C glycosylation depended on the CGT used. The indirect route resulted in mixtures, similar to what has been reported for in vitro experiments. In this case, hydroxylation at the flavonoid 3′-position shifted the ratio towards the 8C-glucosylated orientin. The direct flavone glycosylation by GtUF6CGT1, on the other hand, resulted exclusively in 6C-glucosides.Conclusions: The current study features yeast as a promising host for production of flavone C-glycosides, and it provides a set of tools and strains for identifying and studying CGTs and their mechanisms of C-glycosylation.",
keywords = "Vitexin , Isovitexin, Orientin, Isoorientin , Glycosyl C-transferase , Flavanone 2-hydroxylase",
author = "{Garcia Vanegas}, Katherina and Larsen, {Ar{\'e}su Bondrup} and Michael Eichenberger and David Fischer and Mortensen, {Uffe Hasbro} and Michael Naesby",
note = "Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)",
year = "2018",
doi = "10.1186/s12934-018-0967-y",
language = "English",
volume = "17",
journal = "Microbial Cell Factories",
issn = "1475-2859",
publisher = "BioMed Central",

}

RIS

TY - JOUR

T1 - Indirect and direct routes to C-glycosylated flavones in Saccharomyces cerevisiae 

AU - Garcia Vanegas, Katherina

AU - Larsen, Arésu Bondrup

AU - Eichenberger, Michael

AU - Fischer, David

AU - Mortensen, Uffe Hasbro

AU - Naesby, Michael

N1 - Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)

PY - 2018

Y1 - 2018

N2 - Background: C-glycosylated flavones have recently attracted increased attention due to their possible benefits in human health. These biologically active compounds are part of the human diet, and the C-linkage makes them more resistant to hydrolysis and degradation than O-glycosides. In contrast to O-glycosyltransferases, few C-glycosyltransferases (CGTs) have so far been characterized. Two different biosynthetic routes for C-glycosylated flavones have been identified in plants. Depending on the type of C-glycosyltransferase, flavones can be glycosylated either directly or indirectly via C-glycosylation of a 2-hydroxyflavanone intermediate formed by a flavanone 2-hydroxylase (F2H).Results: In this study, we reconstructed the pathways in the yeast Saccharomyces cerevisiae, to produce some relevant CGT substrates, either the flavanones naringenin and eriodictyol or the flavones apigenin and luteolin. We then demonstrated two-step indirect glycosylation using combinations of F2H and CGT, to convert 2-hydroxyflavanone intermediates into the 6C-glucoside flavones isovitexin and isoorientin, and the 8C-glucoside flavones vitexin and orientin. Furthermore, we established direct glycosylation of flavones using the recently identified GtUF6CGT1 from Gentiana triflora. The ratio between 6C and 8C glycosylation depended on the CGT used. The indirect route resulted in mixtures, similar to what has been reported for in vitro experiments. In this case, hydroxylation at the flavonoid 3′-position shifted the ratio towards the 8C-glucosylated orientin. The direct flavone glycosylation by GtUF6CGT1, on the other hand, resulted exclusively in 6C-glucosides.Conclusions: The current study features yeast as a promising host for production of flavone C-glycosides, and it provides a set of tools and strains for identifying and studying CGTs and their mechanisms of C-glycosylation.

AB - Background: C-glycosylated flavones have recently attracted increased attention due to their possible benefits in human health. These biologically active compounds are part of the human diet, and the C-linkage makes them more resistant to hydrolysis and degradation than O-glycosides. In contrast to O-glycosyltransferases, few C-glycosyltransferases (CGTs) have so far been characterized. Two different biosynthetic routes for C-glycosylated flavones have been identified in plants. Depending on the type of C-glycosyltransferase, flavones can be glycosylated either directly or indirectly via C-glycosylation of a 2-hydroxyflavanone intermediate formed by a flavanone 2-hydroxylase (F2H).Results: In this study, we reconstructed the pathways in the yeast Saccharomyces cerevisiae, to produce some relevant CGT substrates, either the flavanones naringenin and eriodictyol or the flavones apigenin and luteolin. We then demonstrated two-step indirect glycosylation using combinations of F2H and CGT, to convert 2-hydroxyflavanone intermediates into the 6C-glucoside flavones isovitexin and isoorientin, and the 8C-glucoside flavones vitexin and orientin. Furthermore, we established direct glycosylation of flavones using the recently identified GtUF6CGT1 from Gentiana triflora. The ratio between 6C and 8C glycosylation depended on the CGT used. The indirect route resulted in mixtures, similar to what has been reported for in vitro experiments. In this case, hydroxylation at the flavonoid 3′-position shifted the ratio towards the 8C-glucosylated orientin. The direct flavone glycosylation by GtUF6CGT1, on the other hand, resulted exclusively in 6C-glucosides.Conclusions: The current study features yeast as a promising host for production of flavone C-glycosides, and it provides a set of tools and strains for identifying and studying CGTs and their mechanisms of C-glycosylation.

KW - Vitexin

KW - Isovitexin

KW - Orientin

KW - Isoorientin

KW - Glycosyl C-transferase

KW - Flavanone 2-hydroxylase

U2 - 10.1186/s12934-018-0967-y

DO - 10.1186/s12934-018-0967-y

M3 - Journal article

VL - 17

JO - Microbial Cell Factories

JF - Microbial Cell Factories

SN - 1475-2859

M1 - 107

ER -