The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet Building 220, DK-2800 Kgs. Lyngby, Denmark.
Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96, Gothenburg, Sweden.
ACS Synth Biol. 2020 Aug 21;9(8):1978-1988. doi: 10.1021/acssynbio.0c00048. Epub 2020 Jul 27.
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 . Multiple biosynthetic pathway variants, carrying only plant genes or a combination of plant and 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.
迷迭香酸是一种常见的羟基肉桂酸酯，存在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。迷迭香酸可用作食品和化妆品成分，也有一些药物应用的建议。迷迭香酸目前可通过从植物中提取或化学合成来生产；然而，由于植物来源的有限可用性和化学合成方法的复杂性，通过微生物发酵生产这种化合物的兴趣日益增加。在这项研究中，我们旨在通过工程化的酿酒酵母来生产迷迭香酸。使用完全析因设计实验，实施了多个生物合成途径变体，仅携带植物基因或植物和 基因的组合。通过方差分析，评估了每个酶变体（因素）的效果，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了 2.95±0.08mg/L 的迷迭香酸。增加迷迭香酸生物合成基因的拷贝数将产量提高到 5.93±0.06mg/L。该研究表明通过酵母发酵生产迷迭香酸是可行的。
