The marine diatom Phaeodactylum tricornutum is garnering attention as a promising alternative for the production of Biologics, including monoclonal antibodies (mAbs), used to treat severe health conditions. With its remarkable ability to function as a cost-effective cell factory, P. tricornutum has shown potential for industrial applications; nonetheless, the production yield of desired Biologics remains insufficient. Recent meta-analysis of RNA-Seq datasets sheds new insights, paving the way to optimize production strategies and improve yield.
Utilizing publicly available RNA-Seq data from seven strains of Phaeodactylum tricornutum cultured under similar conditions, researchers investigated key biological processes influencing Biologics production. Significant attention was dedicated to the expression of genes involved in the N-glycan biosynthesis, protein export and secretion, as well as quality control and protease activity. The findings are instrumental for future industrial applications, supporting the need to comprehend and control cellular processes.
Firstly, the N-glycosylation process is pivotal as most Biologics are glycoproteins, where the N-glycan structure affects their biological activity and immune response. Analysis revealed differences among strains, with the Pt4 strain displaying favorable characteristics for producing complex-type N-glycans. Researchers highlighted, "Pt3 Ov, Pt4, and Pt8 seemed to be more efficient in the N-glycosylation pathway, Pt3 Ov and Pt4 in protein export and secretion, and Pt3 Tr and Pt3 Fu in quality control and proteasome."
This knowledge is foundational for selecting optimal strains for large-scale production.
The study also evaluated the protein export mechanisms, affirming the significance of secreting recombinant proteins efficiently. Genes related to both co-translational and post-translational protein delivery were found to be expressed at higher levels. Particularly, Pt3 Ov had elevated expression of genes involved, indicating its enhanced capability for protein secretion. The trend indicates the oval morphotype of this strain could lead to higher yields.
Quality control processes play another formidable role, ensuring the correct folding of proteins before they are released. Increased expression of quality control-factor genes was noted across several strains, with Pt4 exhibiting the highest number. Such findings are pivotal since low yields often stem from misfolded proteins.
Interestingly, the meta-analysis showed variations in protease expression, which often contributes to the degradation of mAbs during production. Strains like Pt4 yielded fewer secreted proteases, thereby potentially increasing retention of active Biologics within the culture medium, enhancing overall yield. The authors concluded, "This study confirms existing data which identify the Pt4 strain as the most promising for the production of Biologics."
Researchers are advocating for future investigations targeting the production of antibodies across different ecotypes of P. tricornutum under identical conditions—an effort expected to illuminate potential enhancements to Biologics production efficiencies. By squarely addressing the cellular biology of P. tricornutum, the ultimate goal is not only to understand but also to substantially improve the yield of Biologics derived from this versatile marine diatom.