De Novo Biosynthesis of Caffeic Acid from Glucose by Engineered Saccharomyces cerevisiae. 2020

Yuanzi Li, and Jiwei Mao, and Quanli Liu, and Xiaofei Song, and Yuzhen Wu, and Miao Cai, and Haijin Xu, and Mingqiang Qiao
The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300071, PR China.

Caffeic acid is a plant phenolic compound possessing extensive pharmacological activities. Here, we identified that p-coumaric acid 3-hydroxylase from Arabidopsis thaliana was capable of hydroxylating p-coumaric acid to form caffeic acid in Saccharomyces cerevisiae. Then, we introduced a combined caffeic acid biosynthetic pathway into S. cerevisiae and obtained 0.183 mg L-1 caffeic acid from glucose. Next we improved the tyrosine biosynthesis in S. cerevisiae by blocking the pathway flux to aromatic alcohols and eliminating the tyrosine-induced feedback inhibition resulting in caffeic acid production of 2.780 mg L-1. Finally, the medium was optimized, and the highest caffeic acid production obtained was 11.432 mg L-1 in YPD medium containing 4% glucose. This study opens a route to produce caffeic acid from glucose in S. cerevisiae and establishes a platform for the biosynthesis of caffeic acid derived metabolites.

UI MeSH Term Description Entries
D010940 Plant Proteins Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which PLANT PROTEINS, DIETARY is available. Plant Protein,Protein, Plant,Proteins, Plant
D002109 Caffeic Acids A class of phenolic acids related to chlorogenic acid, p-coumaric acid, vanillic acid, etc., which are found in plant tissues. It is involved in plant growth regulation. Acids, Caffeic
D003373 Coumaric Acids Hydroxycinnamic acid and its derivatives. Act as activators of the indoleacetic acid oxidizing system, thereby producing a decrease in the endogenous level of bound indoleacetic acid in plants. Coumaric Acid,Hydroxycinnamic Acid,Hydroxycinnamic Acids,Acid, Coumaric,Acid, Hydroxycinnamic,Acids, Coumaric,Acids, Hydroxycinnamic
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006899 Mixed Function Oxygenases Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation. Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D017360 Arabidopsis A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development. Arabidopsis thaliana,Cress, Mouse-ear,A. thaliana,A. thalianas,Arabidopses,Arabidopsis thalianas,Cress, Mouse ear,Cresses, Mouse-ear,Mouse-ear Cress,Mouse-ear Cresses,thaliana, A.,thaliana, Arabidopsis,thalianas, A.
D053858 Metabolic Networks and Pathways Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites. Metabolic Networks,Metabolic Pathways,Metabolic Network,Metabolic Pathway,Network, Metabolic,Networks, Metabolic,Pathway, Metabolic,Pathways, Metabolic
D060847 Metabolic Engineering Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS. Engineering, Metabolic

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