College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China.
College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China; State Key Laboratory of Utilization of Woody Oil Resource, Hunan Academy of Forestry, Changsha, Hunan 410004, China.
Bioresour Technol. 2024 Aug;406:130978. doi: 10.1016/j.biortech.2024.130978. Epub 2024 Jun 13.
Cis-13, 16-docosadienoic acid (DDA) is an omega-6 polyunsaturated fatty acid with great potential for application in medicine and health. Using microbial cell factories for DDA production is considered a viable alternative to extracting DDA from plant seeds. In this study, using Yarrowia lipolytica Po1f (Δku70) as a chassis, firstly, the adaptation of three elongases in Po1f (Δku70) were explored. Secondly, the DDA biosynthetic pathway was redesigned, resulting in a DDA content of 0.046 % of total fatty acids (TFAs). Thirdly, through the "push-pull" strategy, the DDA content increased to 0.078 % of TFAs. By enhancing the supply of acetyl-CoA, the DDA production in the engineered strain YL-7 reached 0.391 % of the TFAs (3.19 mg/L). Through optimizing the fermentation conditions, the DDA titer of YL-7 reached 29.34 mg/L. This research achieves the sustainable biological production of DDA in Y. lipolytica.
顺-13,16-二十二碳二烯酸(DDA)是一种具有巨大应用潜力的ω-6 多不饱和脂肪酸,可应用于医学和健康领域。使用微生物细胞工厂生产 DDA 被认为是一种替代从植物种子中提取 DDA 的可行方法。在这项研究中,利用 Yarrowia lipolytica Po1f(Δku70)作为底盘,首先探索了三种延长酶在 Po1f(Δku70)中的适应性。其次,重新设计了 DDA 生物合成途径,使 DDA 含量达到总脂肪酸(TFAs)的 0.046%。第三,通过“推-拉”策略,DDA 含量增加到 TFAs 的 0.078%。通过增强乙酰辅酶 A 的供应,工程菌株 YL-7 中的 DDA 产量达到 TFAs 的 0.391%(3.19mg/L)。通过优化发酵条件,YL-7 的 DDA 产量达到 29.34mg/L。本研究实现了 DDA 在 Yarrowia lipolytica 中的可持续生物生产。