Graduate Program in Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
Xenobiotics Research Unit, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.
PLoS One. 2024 Sep 20;19(9):e0308847. doi: 10.1371/journal.pone.0308847. eCollection 2024.
We evaluated by comparing the performance of three pneumatically-driven bioreactors in the production of L-asparaginase (L-ASNase), an enzyme used to treat leukaemia and lymphoma. A two-step screening process was conducted to detect Cunninghamella spp. strains producing L-ASNase. Cunninghamella echinulata DSM1905 produced the highest levels of L-ASNase during screening assays. Subsequently, fermentations were performed in bubble column (BCR), airlift (ALR), and hybrid fixed-bed airlift (FB-ALR) bioreactors to determine the best upstream bioprocess. Mycelial biomass production was higher in BCR than in ALR and FB-ALR (p ≤ 0.0322). The activity of L-ASNase produced in FB-ALR, in which the fungus grew as a consistent biofilm, was significantly higher (p ≤ 0.022) than that from ALR, which was higher than that of BCR (p = 0.036). The specific activity of ALR and FB-ALR presented no differences (p = 0.073), but it was higher than that of BCR (p ≤ 0.032). In conclusion, C. echinulata DSM1905, grown under the biofilm phenotype, produced the highest levels of L-ASNase, and FB-ALR was the best upstream system for enzyme production.
我们通过比较三种气动驱动生物反应器在生产 L-天冬酰胺酶（L-ASNase）方面的性能来进行评估，L-ASNase 是一种用于治疗白血病和淋巴瘤的酶。我们采用两步筛选法来检测产生 L-ASNase 的 Cunninghamella 菌株。在筛选试验中，发现 C. echinulata DSM1905 产生的 L-ASNase 水平最高。随后，我们在鼓泡塔（BCR）、气升式（ALR）和混合固定床气升式（FB-ALR）生物反应器中进行发酵，以确定最佳的上游生物工艺。与 ALR 和 FB-ALR 相比，BCR 中的菌丝体生物量更高（p ≤ 0.0322）。在 FB-ALR 中，真菌作为一致的生物膜生长，产生的 L-ASNase 活性显著更高（p ≤ 0.022），高于 ALR，而高于 BCR（p = 0.036）。ALR 和 FB-ALR 的比活没有差异（p = 0.073），但高于 BCR（p ≤ 0.032）。总之，C. echinulata DSM1905 在生物膜表型下生长，产生了最高水平的 L-ASNase，而 FB-ALR 是酶生产的最佳上游系统。
