Bioresources and Bioprocessing ( IF 4.3 ) Pub Date : 2023-10-06 , DOI: 10.1186/s40643-023-00689-6 Xin-Ru Zhao 1 , Xin-Liang Chen 1 , Jing-Lin Yang 1 , Qi Gao 1 , Jiang-Ting Shi 1 , Qiang Hua 1, 2 , Liu-Jing Wei 1
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Nervonic acid, a natural fatty acid compound and also a core component of nerve fibers and nerve cells, has been widely used to prevent and treat related diseases of the brain nervous system. At present, fatty acids and their derivatives are mainly obtained by natural extraction or chemical synthesis which are limited by natural resources and production costs. In this study, the de novo synthetic pathway of nervonic acid was constructed in Yarrowia lipolytica by means of synthetic biology, and the yield of nervonic acid was further improved by metabolic engineering and fermentation optimization. Specially, heterologous elongases and desaturases derived from different organism were successfully expressed and evaluated for their potential for the production of nervonic acid in Y. lipolytica. Meanwhile, we overexpressed the genes involved in the lipid metabolism to increase the nervonic acid titer to 111.6 mg/L. In addition, the potential of adding oil as auxiliary carbon sources for nervonic acid production by the engineered Y. lipolytica was analyzed. The results indicated that supplementation with colleseed oil as an auxiliary carbon source can be beneficial for the nervonic acid productivity, which led to the highest concentration of 185.0 mg/L in this work. To summarize, this study describes that the Y. lipolytica can be used as a promising platform for the production of nervonic acid and other very long-chain fatty acids.
Graphical Abstract
中文翻译：
解脂耶氏酵母神经酸的从头合成及代谢调节优化
神经酸是一种天然脂肪酸化合物，也是神经纤维和神经细胞的核心成分，已被广泛用于预防和治疗脑神经系统相关疾病。目前，脂肪酸及其衍生物主要通过天然提取或化学合成获得，受限于自然资源和生产成本。本研究利用合成生物学手段在解脂耶氏酵母中构建了神经酸的从头合成途径，并通过代谢工程和发酵优化进一步提高了神经酸的产率。特别地，源自不同生物体的异源延伸酶和去饱和酶在解脂耶氏酵母中成功表达并评估了它们生产神经酸的潜力。同时，我们过表达参与脂质代谢的基因，将神经酸滴度提高到111.6 mg/L。此外，还分析了添加油作为工程解脂耶氏酵母生产神经酸的辅助碳源的潜力。结果表明，补充菜籽油作为辅助碳源有利于神经酸的生产率，导致本工作中神经酸的最高浓度为185.0 mg/L。总而言之，本研究描述了解脂耶氏酵母可用作生产神经酸和其他极长链脂肪酸的有前途的平台。
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