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.

中文翻译：

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用于生产迷迭香酸的酿酒酵母代谢工程。

迷迭香酸是一种羟基肉桂酸酯，常见于紫草科和唇形科植物中。它具有多种生物活性，包括抗氧化、抗炎、抗菌、抗过敏和抗病毒特性。迷迭香酸用作食品和化妆品成分，并且还提出了几种药物应用。迷迭香酸目前是通过植物提取或化学合成生产的；然而，由于植物来源的有限性和化学合成方法的复杂性，人们越来越关注通过微生物发酵生产这种化合物。在这项研究中，我们旨在通过工程化面包酵母酿酒酵母生产迷迭香酸. 多个生物合成途径变体，仅携带植物基因或植物和大肠杆菌基因的组合，使用全因子实验设计来实施。通过方差分析，评估了每种酶变体（因素）的影响，以及这些因素之间可能的相互作用。最佳途径变体在以葡萄糖为唯一碳源的矿物培养基中产生 2.95 ± 0.08 mg/L 迷迭香酸。增加迷迭香酸生物合成基因的拷贝数将滴度增加到 5.93 ± 0.06 mg/L。研究表明酵母发酵生产迷迭香酸的可行性。