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.

中文翻译：

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酿酒酵母从头开始从葡萄糖生物合成咖啡酸。

咖啡酸是一种具有广泛药理活性的植物酚类化合物。在这里，我们确定了拟南芥中的对香豆酸3-羟化酶能够使对香豆酸羟化，从而在酿酒酵母中形成咖啡酸。然后，我们将咖啡酸的生物合成途径引入了酿酒酵母，并从葡萄糖中获得了0.183 mg L-1咖啡酸。接下来，我们通过阻止通向芳族醇的途径通量并消除酪氨酸诱导的反馈抑制作用，从而导致咖啡酸产生2.780 mg L-1，从而改善了酿酒酵母中酪氨酸的生物合成。最后，对培养基进行了优化，在含4％葡萄糖的YPD培养基中获得的最高咖啡酸产量为11.432 mg L-1。这项研究开辟了一条途径，可以从S中的葡萄糖生产咖啡酸。