The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800, Lyngby, Denmark.
The Bioinformatics Centre, Section for Computational and RNA Biology, Department of Biology, Faculty of Science, University of Copenhagen, Ole Maaloes Vej 5, 2200, Copenhagen, Denmark.
Microb Cell Fact. 2019 Nov 5;18(1):191. doi: 10.1186/s12934-019-1244-4.
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.
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.
The resulting S. cerevisiae strain represents a promising platform host for future production of p-coumaric using xylose as a carbon source.
芳香族氨基酸及其衍生物是有价值的化学品,也是不同工业化合物的前体。对香豆酸是具有商业需求的复杂次生代谢物的主要构建块,如类黄酮和多酚。然而,从酵母中工业规模生产这种化合物仍然具有挑战性。
我们使用代谢工程和系统生物学方法,开发了一种能够从木糖生产 242mg/L 对香豆酸的酿酒酵母平台菌株。当用葡萄糖作为碳源培养时,该菌株仅产生 5.35mg/L。为了进一步表征这个平台菌株,我们进行了转录组分析,比较了该菌株在木糖和葡萄糖上的生长情况,结果显示,当木糖作为碳源时,乙醛酸途径强烈上调,同时细胞壁生物合成增加,出人意料的是芳香族氨基酸基因表达下降。
由此产生的酿酒酵母菌株代表了一种很有前途的平台宿主,可利用木糖作为碳源生产对香豆酸。