Production of novel antioxidative phenolic amides through heterologous expression of the plant’s chlorogenic acid biosynthesis genes in yeast

• Published in: Metabolic engineering Vol. 12; no. 3; pp. 223 - 232
• Main Authors: Andrea, Moglia, Cinzia, Comino, Sergio, Lanteri, Ric, de Vos, Pieter, de Waard, Teris A., van Beek, Luca, Goitre, Saverio Francesco, Retta, Jules, Beekwilder
• Format: Journal Article
• Language: English
• Published: Belgium Elsevier Inc 01.05.2010
• Subjects: 3-Hydroxyanthranilic Acid - metabolism; Amides - metabolism; Animals; Avenanthramide; avenanthramides; cell-suspension cultures; Chlorogenic acid; Chlorogenic Acid - metabolism; Coumaric Acids; Cynara scolymus - genetics; Cynara scolymus - metabolism; escherichia-coli; Esters - metabolism; functional-characterization; Genes; Globe artichoke; liquid-chromatography; Mice; Nicotiana - genetics; Nicotiana - metabolism; Phenols - metabolism; phenylpropanoid metabolism; Plants - enzymology; Plants - genetics; Plants - metabolism; Propionates; purification; recombinant microorganisms; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Yeast; Yeasts - genetics; Yeasts - metabolism; Chlorogenic acid; Yeast; Avenanthramide; Globe artichoke
• ISSN: 1096-7176; 1096-7184
• DOI: 10.1016/j.ymben.2009.11.003

Phenolic esters like chlorogenic acid play an important role in therapeutic properties of many plant extracts. We aimed to produce phenolic esters in baker’s yeast, by expressing tobacco 4CL and globe artichoke HCT. Indeed yeast produced phenolic esters. However, the primary product was identified as N-(E)- p-coumaroyl-3-hydroxyanthranilic acid by NMR. This compound is an amide condensation product of p-coumaric acid, which was supplied to the yeast, with 3-hydroxyanthranilic acid, which was unexpectedly recruited from the yeast metabolism by the HCT enzyme. N-(E)- p-coumaroyl-3-hydroxyanthranilic acid has not been described before, and it shows structural similarity to avenanthramides, a group of inflammation-inhibiting compounds present in oat. When applied to mouse fibroblasts, N-(E)- p-coumaroyl-3-hydroxyanthranilic acid induced a reduction of intracellular reactive oxygen species, indicating a potential therapeutic value for this novel compound.