Process intensification for the protein production from microalgae: a comprehensive review.

Microalgae (predominantly unicellular photosynthetic eukaryotes) has been recognized as a "protein bio-factory" because they may produce up to 70% of protein (dry basis). Advantageous aspects of proteins from microalgae compared to conventional animal- and plant-based proteins were proven. Numerous review articles have addressed the effects of composition of cultivation medium and operational parameters to obtain high protein yield from microalgae. Nevertheless, several critical limitations remain for the industrial expansions of the production of proteins from microalgae. Presently, process intensification is considered a strategic approach for the scalable production of proteins from microalgae, achieved by implementing mutagenic and recombinant strains, increasing productivity through high-cell-density cultivation strategies, using cold-adapted microalgae and minimizing equipment footprint via integrating multiple unit operations into a more efficient and compact system. Different strategies of random mutagenesis (chemical: ethyl methane sulfonate-mediated, physical: heavy-ion irradiation-mediated and ultraviolet-mediated) have been employed to get the desired phenotype of microalgae for higher protein yield. Emerging genetic engineering approaches, including the design of expression vectors, identification of genetic regulatory elements, and genetic transformation methods, along with bioinformatics algorithms, have been employed to develop recombinant strains of microalgae with higher protein yield. Combined cultivation systems, such as sequential heterotrophic-autotrophic system, switching of nitrogen-rich cultivation medium from nitrogen-deficient medium and mixotrophic system have come to the forefront. In this review article, process intensification strategies for the production of proteins from microalgae are comprehensively discussed, with special emphasis on the development of mutant and recombinant strains, strategies of cultivation and decisive operational parameters of bioreactor operation.