Abstract:Fatty acid desaturase, namely Δ12/Δ15 (FADS12/15) are widespread in plants, animals, and microorganisms. They are involved in the biosynthesis of polyunsaturated fatty acids (PUFAs) and play an important role in the production of PUFAs. PUFAs provide various biological and physiological benefits, however, due to the lack of FADS12/15 in the human body, linoleic acid and α?-linolenic acid cannot be synthesized. Therefore, their intake must be derived from the diet. Furthermore, other PUFAs are essential for improving diet and human health. Thus, it is urgent to develop high-level PUFA producers. Microorganisms are potential fatty acid producers, and FADS12/15 genetic engineering has been performed to increase the yield of ω-3/ω-6 PUFAs, which provide humans with high-quality lipid resources. This article summarizes the fatty acid biosynthetic pathways and the catalytic mechanism of FADS12/15. It also reviews FADS12/15 overexpression system and genetically engineered microorganisms for PUFA production as well as the homologous or heterologous expression of FADS12/15 gene to produce PUFAs. The objective of this review is to provide the fundamental theory and efficient expression strategy for FADS12/15 genetic engineering to produce PUFAs.