Long-chain polyunsaturated fatty acids (LC-PUFAs) especially ω-3 fatty acids provide significant health benefits for human beings. However, ω-3 LC-PUFAs cannot be synthesized de novo in mammals. Traditionally, ω-3 LC-PUFAs are extracted from marine fish, and their production depends on sea fishing, which has not met ever-increasing global demand. To address the challenges, innovative cellular engineering strategies need to be developed. In nature, many fungi and microalgae are rich in ω-3 LC-PUFAs, representing promising sources of ω-3 LC-PUFAs. The latest progress in developing new cellular engineering strategies toward sustainable ω-3 LC-PUFAs production using fungi and microalga has demonstrated that they can to some extent address the supply shortage. In this review, we critically summarize the recent progress in enhancing the productivity in various ω-3 LC-PUFAs-producing organisms, as well as the latest efforts of biosynthesizing PUFAs in heterogenous biosystems. In addition, we also provide future perspectives in developing genetic toolkits for LC-PUFAs producing microbes so that cut-edging biotechnology such as gene stacking and genome editing can be further applied to increase the productivity of ω-3 LC-PUFAs.

长链多不饱和脂肪酸（LC-PUFA），尤其是ω-3脂肪酸，对人类具有显着的健康益处。但是，ω-3LC-PUFA不能从头合成在哺乳动物中。传统上，ω-3LC-PUFAs是从海鱼中提取的，其生产依赖于海洋捕捞，而海洋捕捞并不能满足日益增长的全球需求。为了应对挑战，需要开发创新的细胞工程策略。在自然界中，许多真菌和微藻富含ω-3LC-PUFA，代表了有希望的ω-3LC-PUFA来源。利用真菌和微藻开发新的细胞工程策略以可持续生产ω-3LC-PUFAs的最新进展表明，它们可以在一定程度上解决供应短缺的问题。在这篇综述中，我们批判性地总结了提高各种ω-3LC-PUFAs生产生物的生产力方面的最新进展，以及在异质生物系统中生物合成PUFAs的最新成果。此外，