Optimized production of a bioactive human recombinant protein from the microalgae Chlamydomonas reinhardtii grown at high density in a fed-batch bioreactor

• Published in: Algal research (Amsterdam) 2022-07, Vol.66, p.102786, Article 102786
• Main Authors: Torres-Tiji, Yasin, Fields, Francis J., Yang, Yanping, Heredia, Vanessa, Horn, Svein Jarle, Keremane, Saumya R., Jin, Moonsoo M., Mayfield, Stephen P.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; algae; bioproducts; Bioreactor; biotechnology; Chlamydomonas reinhardtii; co-products; High yield; high-value; ICAM-1; Microalgae; Recombinant protein
• ISSN: 2211-9264; 2211-9264
• DOI: 10.1016/j.algal.2022.102786

Microalgae have been identified as an alternative platform to produce high-quality biomass and subsequent bioproducts, such as foods, feeds, nutritional supplements, recombinant proteins, and biofuels. Traditional biotechnological hosts for therapeutic proteins, such as the bacteria Escherichia coli and mammalian CHO cells, have long been established as the dominate platforms, but recent advances have shown that microalgae can potentially serve as an alternative platform. In the present study, we examine the potential of the microalga Chlamydomonas reinhardtii to produce a complex human recombinant protein in a high-density heterotrophic culture. The recombinant human protein, ICAM-1, was targeted for secretion to the extracellular media of the culture from cells grown in a bioreactor using a fed-batch strategy to achieve high cell density. Ultimately, this resulted in a maximum biomass titer of 40 g/L and a recombinant protein titer of 50 mg/L. The algal-produced ICAM-1 protein showed comparable bioactivity to mammalian cell culture produced ICAM-1, as measured using binding assays for its native ligand LFA-1. This work shows that C. reinhardtii is a viable option to produce complex recombinant proteins, with native biological activity, at high concentrations using a fed batch heterotrophic growth strategy. [Display omitted] •Improved Chlamydomonas reinhardtii biomass accumulation in a bioreactor.•Recombinant production of human ICAM-1 in Chlamydomonas reinhardtii•Optimization of algal heterotrophic fed-batch for recombinant protein production•Algal produced ICAM-1 shows similar biological activity to the mammalian version.