Sustainable Microbial Production and Application of DHA: From Laboratory to Shelf.

Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), is essential for neural development, cardiovascular protection, and anti-inflammation. Conventional fish-oil supply chains remain vulnerable to ecological pressure, compositional variability, and contaminants. Microbial production offers a controllable alternative, yet commercial feasibility depends on numerous factors beyond the strain yield. This review summarizes DHA-producing microorganisms and their metabolic pathways, including precursor supply, biosynthetic and storage pathways, and downstream separation and purification. Various separation strategies, ranging from crude lipid extraction to high-purity DHA, are evaluated in terms of recovery, selectivity, scale, cost, and oxidation risk. We discussed the synergistic mixed-fermentation and refining strategy that coproduces carotenoids, astaxanthin, and FAs to enhance the economic value. To achieve commercial competitiveness, a comprehensive approach combining metabolic engineering, fermentation optimization, and separation engineering is required to establish a microbial platform as an environmentally friendly and sustainable alternative to DHA from animal sources.