Boulogne Isabelle, Toustou Charlotte, Bardor Muriel
University of Rouen Normandie, UNIROUEN, UFR des Sciences et Techniques, GlycoMEV UR4358, Innovation Chimie Carnot, Fédération de Recherche Normandie-Végétal FED 4277, 76821, Mont-Saint-Aignan, France.
ECOTERCA - ÉCOlogie TERrestre CAribéenne, Université des Antilles, Faculté des Sciences Exactes et Naturelles, Campus de Fouillole, BP 592, 97159, Pointe-à-Pitre Cedex, France.
Sci Rep. 2025 Jan 29;15(1):3603. doi: 10.1038/s41598-025-87620-5.
The marine diatom Phaeodactylum tricornutum is currently used for various industrial applications, including the pharmaceutical industry as a cost-effective cell biofactory to produce Biologics. Recent studies demonstrated that P. tricornutum can produce functional monoclonal antibodies, such application is currently limited by the production yield that hinders industrialization. Therefore, it is necessary to understand and control the cell biology of P. tricornutum to improve the Biologics production yield. Transcriptomic analyses have recently been used by the pharmaceutical industry to improve the production of Biologics in mammalian cells, especially Biologics titer and cell productivity. Hence, in the present work, we performed a meta-analysis of seven publicly available RNA-Seq datasets from different strains of P. tricornutum, for which the culture conditions were chosen as similar as possible. We analyzed the differential expression of genes that are involved in biological processes that are well known to potentially impact the bioproduction and critical quality attributes of Biologics. Therefore, the expression of genes involved in the N-glycan biosynthesis, protein export and secretion, protein quality control and proteasome, as well as those encoding proteases were analyzed and compared. The results pave the way towards optimizing Biologics production in P. tricornutum and highlight that the Pt4, Pt3 Ov and Pt8 strains seem to be the most promising P. tricornutum strains.
海洋硅藻三角褐指藻目前被用于各种工业应用，包括制药行业，作为一种具有成本效益的细胞生物工厂来生产生物制品。最近的研究表明，三角褐指藻能够产生功能性单克隆抗体，但目前这种应用受到产量的限制，阻碍了其工业化进程。因此，有必要了解和控制三角褐指藻的细胞生物学特性，以提高生物制品的产量。制药行业最近利用转录组分析来提高哺乳动物细胞中生物制品的产量，特别是生物制品滴度和细胞生产力。因此，在本研究中，我们对来自不同三角褐指藻菌株的七个公开可用的RNA-Seq数据集进行了荟萃分析，这些数据集的培养条件尽可能相似。我们分析了参与生物过程的基因的差异表达，这些生物过程可能会对生物制品的生物生产和关键质量属性产生潜在影响。因此，对参与N-聚糖生物合成、蛋白质输出和分泌、蛋白质质量控制和蛋白酶体的基因表达，以及那些编码蛋白酶的基因表达进行了分析和比较。这些结果为优化三角褐指藻中生物制品的生产铺平了道路，并突出表明Pt4、Pt3 Ov和Pt8菌株似乎是最有前景的三角褐指藻菌株。
