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在气动驱动生物反应器中基于 Cunninghamella echinulata DSM1905 生物膜的 L-天冬酰胺酶生产。

Cunninghamella echinulata DSM1905 biofilm-based L-asparaginase production in pneumatically-driven bioreactors.

机构信息

Graduate Program in Dentistry, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Xenobiotics Research Unit, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

出版信息

PLoS One. 2024 Sep 20;19(9):e0308847. doi: 10.1371/journal.pone.0308847. eCollection 2024.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e3f/11414969/84eb6f6a4dbd/pone.0308847.g001.jpg

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