Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis
Abstract 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 pl...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Microbial Cell Factories |
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| Online Access: | https://doi.org/10.1186/s12934-024-02356-7 |
| _version_ | 1797258921318023168 |
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| author | Asmaa Gamal Eman Fikry Nora Tawfeek Azza M. El-Shafae Ashraf S. A. El-Sayed Maher M. El-Domiaty |
| author_facet | Asmaa Gamal Eman Fikry Nora Tawfeek Azza M. El-Shafae Ashraf S. A. El-Sayed Maher M. El-Domiaty |
| author_sort | Asmaa Gamal |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T23:01:13Z |
| format | Article |
| id | doaj.art-21c61d8038084d30a6111f5f260294da |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-24T23:01:13Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-21c61d8038084d30a6111f5f260294da2024-03-17T12:42:52ZengBMCMicrobial Cell Factories1475-28592024-03-0123111910.1186/s12934-024-02356-7Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysisAsmaa Gamal0Eman Fikry1Nora Tawfeek2Azza M. El-Shafae3Ashraf S. A. El-Sayed4Maher M. El-Domiaty5Pharmacognosy Department, Faculty of Pharmacy, Zagazig UniversityPharmacognosy Department, Faculty of Pharmacy, Zagazig UniversityPharmacognosy Department, Faculty of Pharmacy, Zagazig UniversityPharmacognosy Department, Faculty of Pharmacy, Zagazig UniversityEnzymology and Fungal Biotechnology Lab, Botany and Microbiology Department, Faculty of Science, Zagazig UniversityPharmacognosy Department, Faculty of Pharmacy, Zagazig UniversityAbstract 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.https://doi.org/10.1186/s12934-024-02356-7TaxolAspergillus nigerEncephalartos whitelockiiAntiproliferative activityWound healingCell cycle analysis |
| spellingShingle | Asmaa Gamal Eman Fikry Nora Tawfeek Azza M. El-Shafae Ashraf S. A. El-Sayed Maher M. El-Domiaty 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 Taxol Aspergillus niger Encephalartos whitelockii Antiproliferative activity Wound healing Cell cycle analysis |
| title | Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis |
| title_full | Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis |
| title_fullStr | Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis |
| title_full_unstemmed | Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis |
| title_short | Production and bioprocessing of Taxol from Aspergillus niger, an endophyte of Encephalartos whitelockii, with a plausible biosynthetic stability: antiproliferative activity and cell cycle analysis |
| title_sort | production and bioprocessing of taxol from aspergillus niger an endophyte of encephalartos whitelockii with a plausible biosynthetic stability antiproliferative activity and cell cycle analysis |
| topic | Taxol Aspergillus niger Encephalartos whitelockii Antiproliferative activity Wound healing Cell cycle analysis |
| url | https://doi.org/10.1186/s12934-024-02356-7 |
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