Evaluation of the bioactive properties of avenanthramide analogs produced in recombinant yeast

Andrea Moglia, Luca Goitre, Silvia Gianoglio, Jules Beekwilder

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Saccharomyces cerevisiae has been proven to be a valuable tool for the expression of plant metabolic pathways. By engineering a S. cerevisiae strain with two plant genes (4cl-2 from tobacco and hct from globe artichoke) we previously set up a system for the production of two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, Yav I) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, Yav II). These compounds have a structural similarity with a class of bioactive oat compounds called avenanthramides. By developing a fermentation process for the engineered S. cerevisiae strain, we obtained a high-yield production of Yav I and Yav II. To examine the biological relevance of these compounds, we tested their potential antioxidant and antiproliferative properties upon treatment of widely used cell models, including immortalized mouse embryonic fibroblast cell lines and HeLa cancer cells. The outcomes of our experiments showed that both Yav I and Yav II enter the cell and trigger a significant up-regulation of master regulators of cell antioxidant responses, including the major antioxidant protein SOD2 and its transcriptional regulator FoxO1 as well as the down-regulation of Cyclin D1. Intriguingly, these effects were also demonstrated in cellular models of the human genetic disease Cerebral Cavernous Malformation, suggesting that the novel phenolic compounds Yav I and Yav II are endowed with bioactive properties relevant to biomedical applications. Taken together, our data demonstrate the feasibility of biotechnological production of yeast avenanthramides and underline a biologically relevant antioxidant activity of these molecules.

LanguageEnglish
Pages15-27
JournalBioFactors
Volume41
Issue number1
DOIs
Publication statusPublished - 2015

Fingerprint

Yeast
Yeasts
3-Hydroxyanthranilic Acid
Antioxidants
Saccharomyces cerevisiae
Central Nervous System Cavernous Hemangioma
Cynara scolymus
avenanthramide-2C
Plant Genes
Cells
Inborn Genetic Diseases
Cyclin D1
Medical Genetics
Metabolic Networks and Pathways
HeLa Cells
Tobacco
Fermentation
Fibroblasts
Up-Regulation
Down-Regulation

Keywords

  • Antioxidants
  • Avenanthramides
  • Biofactors
  • Cerebral cavernous malformation
  • Metabolic engineering
  • Phenolic compounds
  • Plant secondary metabolites
  • Saccharomyces cerevisiae

Cite this

Moglia, Andrea ; Goitre, Luca ; Gianoglio, Silvia ; Beekwilder, Jules. / Evaluation of the bioactive properties of avenanthramide analogs produced in recombinant yeast. In: BioFactors. 2015 ; Vol. 41, No. 1. pp. 15-27.
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Evaluation of the bioactive properties of avenanthramide analogs produced in recombinant yeast. / Moglia, Andrea; Goitre, Luca; Gianoglio, Silvia; Beekwilder, Jules.

In: BioFactors, Vol. 41, No. 1, 2015, p. 15-27.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Evaluation of the bioactive properties of avenanthramide analogs produced in recombinant yeast

AU - Moglia, Andrea

AU - Goitre, Luca

AU - Gianoglio, Silvia

AU - Beekwilder, Jules

PY - 2015

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N2 - Saccharomyces cerevisiae has been proven to be a valuable tool for the expression of plant metabolic pathways. By engineering a S. cerevisiae strain with two plant genes (4cl-2 from tobacco and hct from globe artichoke) we previously set up a system for the production of two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, Yav I) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, Yav II). These compounds have a structural similarity with a class of bioactive oat compounds called avenanthramides. By developing a fermentation process for the engineered S. cerevisiae strain, we obtained a high-yield production of Yav I and Yav II. To examine the biological relevance of these compounds, we tested their potential antioxidant and antiproliferative properties upon treatment of widely used cell models, including immortalized mouse embryonic fibroblast cell lines and HeLa cancer cells. The outcomes of our experiments showed that both Yav I and Yav II enter the cell and trigger a significant up-regulation of master regulators of cell antioxidant responses, including the major antioxidant protein SOD2 and its transcriptional regulator FoxO1 as well as the down-regulation of Cyclin D1. Intriguingly, these effects were also demonstrated in cellular models of the human genetic disease Cerebral Cavernous Malformation, suggesting that the novel phenolic compounds Yav I and Yav II are endowed with bioactive properties relevant to biomedical applications. Taken together, our data demonstrate the feasibility of biotechnological production of yeast avenanthramides and underline a biologically relevant antioxidant activity of these molecules.

AB - Saccharomyces cerevisiae has been proven to be a valuable tool for the expression of plant metabolic pathways. By engineering a S. cerevisiae strain with two plant genes (4cl-2 from tobacco and hct from globe artichoke) we previously set up a system for the production of two novel phenolic compounds, N-(E)-p-coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, Yav I) and N-(E)-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, Yav II). These compounds have a structural similarity with a class of bioactive oat compounds called avenanthramides. By developing a fermentation process for the engineered S. cerevisiae strain, we obtained a high-yield production of Yav I and Yav II. To examine the biological relevance of these compounds, we tested their potential antioxidant and antiproliferative properties upon treatment of widely used cell models, including immortalized mouse embryonic fibroblast cell lines and HeLa cancer cells. The outcomes of our experiments showed that both Yav I and Yav II enter the cell and trigger a significant up-regulation of master regulators of cell antioxidant responses, including the major antioxidant protein SOD2 and its transcriptional regulator FoxO1 as well as the down-regulation of Cyclin D1. Intriguingly, these effects were also demonstrated in cellular models of the human genetic disease Cerebral Cavernous Malformation, suggesting that the novel phenolic compounds Yav I and Yav II are endowed with bioactive properties relevant to biomedical applications. Taken together, our data demonstrate the feasibility of biotechnological production of yeast avenanthramides and underline a biologically relevant antioxidant activity of these molecules.

KW - Antioxidants

KW - Avenanthramides

KW - Biofactors

KW - Cerebral cavernous malformation

KW - Metabolic engineering

KW - Phenolic compounds

KW - Plant secondary metabolites

KW - Saccharomyces cerevisiae

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VL - 41

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JO - BioFactors

T2 - BioFactors

JF - BioFactors

SN - 0951-6433

IS - 1

ER -