Zhang Zi-Xu, Wu Hong-Xuan, Lin Yan-Cheng, Xu Ying-Shuang, Ma Wang, Sun Xiao-Man, Huang He
School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, 2 Xuelin Road, Qixia District, Nanjing 210023, China.
J Agric Food Chem. 2025 Jan 29;73(4):2461-2470. doi: 10.1021/acs.jafc.4c10465. Epub 2024 Dec 23.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are important polyunsaturated fatty acids (PUFAs) used as nutritional supplements. The natural EPA content in sp. is low, and traditional strategies to increase EPA levels often compromise DHA content or lipid accumulation, hindering industrial coproduction. This study aims to modify the PUFA synthase pathway in sp. to enable high levels of EPA accumulation while maintaining high levels of DHA production. The native acyltransferase (AT) domain in the PKS subunit was replaced with an EPA-specific AT, increasing the EPA content nearly five-fold (3.94%). Additionally, adding food-grade phenolic compounds to boost EPA accumulation and overexpressing C16 elongase to alleviate lipid synthesis inhibition increased the EPA content from 0.80 to 7.86% in a 5L bioreactor. Ultimately, EPA and DHA titers reached 3.79 and 22.06 g/L, respectively. These findings highlight the potential of sp. as an efficient cell factory for sustainable EPA and DHA coproduction on an industrial scale.
二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）是用作营养补充剂的重要多不饱和脂肪酸（PUFA）。 种中的天然EPA含量较低，而增加EPA水平的传统策略往往会影响DHA含量或脂质积累，从而阻碍工业联产。本研究旨在改造 种中的PUFA合酶途径，以实现高水平的EPA积累，同时保持高水平的DHA产量。将PKS亚基中的天然酰基转移酶（AT）结构域替换为EPA特异性AT，使EPA含量增加了近五倍（3.94%）。此外，添加食品级酚类化合物以促进EPA积累，并过表达C16延长酶以减轻脂质合成抑制，在5L生物反应器中将EPA含量从0.80%提高到7.86%。最终，EPA和DHA的滴度分别达到3.79 g/L和22.06 g/L。这些发现突出了 种作为工业规模可持续联产EPA和DHA的高效细胞工厂的潜力。
