Microbial cell factories for gamma-linolenic acid biosynthesis: metabolic engineering, downstream processing, and future perspectives

Gamma-linolenic acid (GLA) is a vital anti-inflammatory polyunsaturated fatty acid, yet its traditional supply from plant seeds such as evening primrose and borage is constrained by low yields and climatic instability. Consequently, microbial cell factories present a sustainable and season-independent alternative for scalable GLA production. This review critically synthesizes recent biotechnological advancements in utilizing oleaginous microorganisms as production platforms. It systematically elucidates the microbial lipid biosynthesis pathways and evaluates strategies to enhance GLA accumulation, with particular emphasis on rational metabolic engineering. Furthermore, emerging technologies for microbial lipid production, alongside the latest progress in industrial-scale applications, are thoroughly examined. Finally, comprehensive insights are provided to guide the optimization of the entire value chain, ranging from upstream strain engineering to downstream processing.