| 1. |
- Babaei, Mahsa, et al.
(författare)
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Metabolic Engineering of Saccharomyces cerevisiae for Rosmarinic Acid Production
- 2020
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Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 9:8, s. 1978-1988
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Tidskriftsartikel (refereegranskat)abstract
- Rosmarinic acid is a hydroxycinnamic acid ester commonly found in the Boraginaceae and Lamiaceae plant families. It exhibits various biological activities, including antioxidant, anti-inflammatory, antibacterial, antiallergic, and antiviral properties. Rosmarinic acid is used as a food and cosmetic ingredient, and several pharmaceutical applications have been suggested as well. Rosmarinic acid is currently produced by extraction from plants or chemical synthesis; however, due to limited availability of the plant sources and the complexity of the chemical synthesis method, there is an increasing interest in producing this compound by microbial fermentation. In this study, we aimed to produce rosmarinic acid by engineered baker's yeast Saccharomyces cerevisiae. Multiple biosynthetic pathway variants, carrying only plant genes or a combination of plant and Escherichia coli genes, were implemented using a full factorial design of experiment. Through analysis of variances, the effect of each enzyme variant (factors), together with possible interactions between these factors, was assessed. The best pathway variant produced 2.95 ± 0.08 mg/L rosmarinic acid in mineral medium with glucose as the sole carbon source. Increasing the copy number of rosmarinic acid biosynthetic genes increased the titer to 5.93 ± 0.06 mg/L. The study shows the feasibility of producing rosmarinic acid by yeast fermentation.
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| 2. |
- Borja, Gheorghe M., et al.
(författare)
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Metabolic engineering and transcriptomic analysis of Saccharomyces cerevisiae producing p-coumaric acid from xylose
- 2019
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Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aromatic amino acids and their derivatives are valuable chemicals and are precursors for different industrially compounds. p-Coumaric acid is the main building block for complex secondary metabolites in commercial demand, such as flavonoids and polyphenols. Industrial scale production of this compound from yeast however remains challenging. Results: Using metabolic engineering and a systems biology approach, we developed a Saccharomyces cerevisiae platform strain able to produce 242 mg/L of p-coumaric acid from xylose. The same strain produced only 5.35 mg/L when cultivated with glucose as carbon source. To characterise this platform strain further, transcriptomic analysis was performed, comparing this strain's growth on xylose and glucose, revealing a strong up-regulation of the glyoxylate pathway alongside increased cell wall biosynthesis and unexpectedly a decrease in aromatic amino acid gene expression when xylose was used as carbon source. Conclusions: The resulting S. cerevisiae strain represents a promising platform host for future production of p-coumaric using xylose as a carbon source.
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