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Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis
Microbial Cell Factories ( IF 6.4 ) Pub Date : 2024-03-12 , DOI: 10.1186/s12934-024-02356-7
Asmaa Gamal , Eman Fikry , Nora Tawfeek , Azza M. El-Shafae , Ashraf S. A. El-Sayed , Maher M. El-Domiaty

The biosynthetic potency of Taxol by fungi raises their prospective to be a platform for commercial production of Taxol, nevertheless, the attenuation of its productivity with the fungal storage, is the challenge. Thus, screening for a novel fungal isolate inhabiting ethnopharmacological plants, with a plausible metabolic stability for Taxol production could be one of the most affordable approaches. Aspergillus niger OR414905.1, an endophyte of Encephalartos whitelockii, had the highest Taxol productivity (173.9 μg/L). The chemical identity of the purified Taxol was confirmed by HPLC, FTIR, and LC–MS/MS analyses, exhibiting the same molecular mass (854.5 m/z) and molecular fragmentation pattern of the authentic Taxol. The purified Taxol exhibited a potent antiproliferative activity against HepG-2, MCF-7 and Caco-2, with IC50 values 0.011, 0.016, and 0.067 μM, respectively, in addition to a significant activity against A. flavus, as a model of human fungal pathogen. The purified Taxol displayed a significant effect against the cellular migration of HepG-2 and MCF-7 cells, by ~ 52–59% after 72 h, compared to the control, confirming its interference with the cellular matrix formation. Furthermore, the purified Taxol exhibited a significant ability to prompt apoptosis in MCF-7 cells, by about 11-fold compared to control cells, suppressing their division at G2/M phase. Taxol productivity by A. niger has been optimized by the response surface methodology with Plackett–Burman Design and Central Composite Design, resulting in a remarkable ~ 1.6-fold increase (279.8 μg/L), over the control. The biological half-life time of Taxol productivity by A. niger was ~ 6 months of preservation at 4 ℃, however, the Taxol yield by A. niger was partially restored in response to ethyl acetate extracts of E. whitelockii, ensuring the presence of plant-derived signals that triggers the cryptic Taxol encoding genes.

中文翻译:

从黑曲霉(Encephalartos Whitelockii 的内生菌)中生产和生物加工紫杉醇,具有合理的生物合成稳定性:抗增殖活性和细胞周期分析

真菌对紫杉醇的生物合成效力提高了其成为紫杉醇商业化生产平台的前景,然而,其生产力因真菌储存而减弱是一个挑战。因此,筛选居住在民族药理学植物中的新型真菌分离株,其对紫杉醇生产具有合理的代谢稳定性可能是最经济的方法之一。黑曲霉 OR414905.1 是 Encephalartos Whitelockii 的内生真菌,其紫杉醇生产率最高(173.9 μg/L)。通过 HPLC、FTIR 和 LC-MS/MS 分析证实了纯化紫杉醇的化学特性,显示出与正品紫杉醇相同的分子量 (854.5 m/z) 和分子碎片模式。纯化的紫杉醇对 HepG-2、MCF-7 和 Caco-2 表现出有效的抗增殖活性,IC50 值分别为 0.011、0.016 和 0.067 μM,此外还对人类模型黄曲霉具有显着的活性。真菌病原体。与对照相比,纯化的紫杉醇对 HepG-2 和 MCF-7 细胞的细胞迁移具有显着的抑制作用,72 小时后抑制效果达 52-59%,证实了其对细胞基质形成的干扰。此外,纯化的紫杉醇表现出显着的促进 MCF-7 细胞凋亡的能力,与对照细胞相比约 11 倍,抑制其 G2/M 期分裂。黑曲霉的紫杉醇生产率已通过 Plackett-Burman 设计和中心复合设计的响应面方法进行了优化,与对照相比,显着提高了约 1.6 倍(279.8 μg/L)。在 4 ℃ 保存下,黑曲霉产生的紫杉醇生产力的生物半衰期约为 6 个月,然而,黑曲霉的紫杉醇产量响应 E. Whitelockii 的乙酸乙酯提取物而部分恢复,确保了存在植物来源的信号触发神秘的紫杉醇编码基因。
更新日期:2024-03-13
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