Engineering Approaches for Sustainable Protein Production in Microalgae: A Comprehensive Review

The continuously growing demand for dietary protein raises the urgency of expanding supply chains beyond conventional animal-based sources. Microalgae are well-known as biofactories due to their high photosynthetic efficiency, rapid growth, minimal resource requirements, and ability to thrive in diverse environments. To maximize protein production, mixotrophic cultivation is often preferred, as it enables significantly higher biomass yields. Key factors, including light quality (intensity and wavelength), carbon sources (inorganic CO₂ and organic substrates), and nitrogen availability, play significant roles in directing metabolic fluxes toward protein biosynthesis, the modulation of which refers to biochemical engineering. In the field of genetic engineering, precise gene editing tools, especially CRISPR/Cas9, have demonstrated considerable promise, although the application in enhancing microalgal protein production remains challenging and limited. By contrast, random mutagenesis has been proven effective in improving multiple strains for increased protein accumulation. Beyond upstream strategies, downstream engineering, including drying, extrusion forming, and fermentation, is emphasized for improving the nutritional and functional properties of microalgal proteins for food and feed applications in the form of whole cells. Furthermore, extracted microalgal proteins broaden the range of potential applications, whose quality is significantly affected by the methods used for cell disruption/extraction, purification, and hydrolysis. Novel biorefinery strategies are also discussed to enhance economic viability by integrating value-added biomass utilization within a protein-first recovery scheme. Altogether, by combining advances in cultivation technologies, strain modification, processing, and supportive policy frameworks, this review supports the development of sustainable protein production platforms based on microalgae.