Abstract
Microalgae exhibit great potential for recombinant therapeutic protein production, due to lower production costs, immunity to human pathogens, and advanced genetic toolkits. However, a fundamental aspect to consider for recombinant biopharmaceutical production is the presence of correct post-translational modifications. Multiple recent studies focusing on glycosylation in microalgae have revealed unique species-specific patterns absent in humans. Glycosylation is particularly important for protein function and is directly responsible for recombinant biopharmaceutical immunogenicity. Therefore, it is necessary to fully characterise this key feature in microalgae before these organisms can be established as industrially relevant microbial biofactories. Here, we review the work done to date on production of recombinant biopharmaceuticals in microalgae, experimental and computational evidence for N- and O-glycosylation in diverse microalgal groups, established approaches for glyco-engineering, and perspectives for their application in microalgal systems. The insights from this review may be applied to future glyco-engineering attempts to humanize recombinant therapeutic proteins and to potentially obtain cheaper, fully functional biopharmaceuticals from microalgae.
Highlights
Biopharmaceuticals are biological macromolecules that exhibit therapeutic actions in humans.This group of compounds includes essential molecules such as antibodies, hormones, and vaccines [1].More than 60% of commercialized biopharmaceuticals are recombinant proteins [2], which are produced in genetically engineered host cells defined as biofactories [3]
We provide a brief overview of various host systems, with a focus on the advantages and disadvantages of microalgae as biofactories for the production of recombinant therapeutic proteins
As increasing knowledge and genetic tools become available, other microalgae species have been exploited for recombinant protein production, including monoclonal antibodies, hormones, and enzymes
Summary
Biopharmaceuticals are biological macromolecules that exhibit therapeutic actions in humans. Biopharmaceutical production with CHO cells is expensive because of the complex culturing requirements associated, difficult to scale, and susceptible to contamination with human viruses and prions [9,10] These complications have prompted efforts to optimize these systems as well as identify more suitable host cell lines. A major challenge with producing biopharmaceuticals in non-human cells is obtaining correct post-translational modifications (PTMs) of the recombinant protein. Given the significant influence of glycosylation on yield, efficacy, pharmacokinetics, and immunogenicity of recombinant therapeutic proteins, it is essential to choose the right host expression system to successfully produce a functional biopharmaceutical [30]. We assess the prospect of applying glyco-engineering techniques to optimize recombinant biopharmaceutical production in microalgal host systems
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