Sustainable microbial and microalgal production of omega-3 fatty acids: cultivation strategies, sustainable substrates, and waste valorization

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are important bioactive lipids that play critical roles in cardiovascular, neurological, visual, and immune health. Although humans can synthesize EPA and DHA from shorter-chain precursors, endogenous conversion is limited, making dietary intake an important source of these long-chain fatty acids. Fish oil remains the predominant commercial source of EPA and DHA; however, declining fish stocks, overfishing, marine pollution, and climate change have raised concerns regarding the sustainability, safety, and long-term availability of conventional marine sources. Consequently, microorganisms, including bacteria, microalgae, dinoflagellates, thraustochytrids, and other oleaginous protists, have emerged as promising alternative sources of omega-3 PUFAs. This review provides a comprehensive overview of microbial and microalgal platforms for large-scale EPA and DHA production, focusing on cultivation strategies, lipid extraction and purification, and factors influencing product stability and bioavailability. The potential of inexpensive and sustainable substrates derived from agricultural residues, food-processing by-products, waste oils, and wastewater is also discussed in the context of waste valorization and the circular bioeconomy. Furthermore, the health benefits, advantages, limitations, and technological challenges associated with microbial and microalgal omega-3 production are critically evaluated, along with emerging strategies for improving productivity, process sustainability, and commercial feasibility.