Bioprocesses optimization and anticancer activity of camptothecin from Aspergillus flavus, an endophyte of in vitro cultured Astragalus fruticosus

Elsayed, Abdelrahman H.; Zayed, Rawia; El-Baz, Ashraf F.; Ismaeil, Wafaa M.

doi:10.1007/s11033-022-07271-x

Cited by 18 publications

(40 citation statements)

References 58 publications

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“…As well as, several isolates of A. flavus inhabiting leaves and stems of C. diurnum and C. elegans exhibiting a mild camptothecin productivities (40–60 µg/L). Several paradigm of screening for camptothecin productivity has been reported by our previous studies [ 10 , 34 ]. Interestingly, isolates of Aspergillus terreus as endophytes of from different plants have been reported frequently camptothecin producers [ 10 ], ensuring the efficiency of the molecular machinery of camptothecin productivity by A. terreus , as common mechanisms for plant defense, and common fungal-plant interaction.…”

Section: Resultsmentioning

confidence: 99%

“…#959963-902), using isocratic mobile phase methanol/ water (60:40 v/v) at a flow rate 1.0 mL/min for 20 min, scanned by photodiode array detector (DAD). The identity and concentration of the putative sample of camptothecin were confirmed from retention time and peak area, normalizing to the authentic one at λ360 nm [ 34 , 35 ].…”

Section: Methodsmentioning

confidence: 99%

“…The chemical identity of camptothecin was verified by liquid chromatography tandem mass spectrometry (LC–MS/MS) with Thermo Scientific LCQ Deca mass spectrometer and Hypersil Gold C18 column, with an electrospray source in positive and negative ion modes. The mobile phases A (0.1% formic acid), and B (acetonitrile in 0.1% formic acid) were used [ 10 , 34 , 35 ]. The gradient elution system was 2–98% mobile phase B over 30 min at a flow rate of 0.2 mL/min for 40 min.…”

Section: Methodsmentioning

confidence: 99%

“…Various physicochemical parameters, acid whey, malt extract, potato starch, methyljasmonate, tryptamine, peptone, dextrin, tryptone, glucose, salicylic acid, tryptophan, serine, cysteine, pyruvate, phenylalanine, glutamate and fluconazole were optimized by Plackett–Burman design to maximize the yield of camptothecin from the target fungus [ 10 , 34 , 35 ]. The nineteen parameters were screened by two variables of Plackett–Burman design, each represented by high (+ 1) and low (− 1) levels, according to the first order reaction: where, Y is the predicted yield of camptothecin, Xi is an independent variable, b i is the linear coefficient, and b 0 is the model intercept.…”

Section: Methodsmentioning

confidence: 99%

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Production and bioprocessing of camptothecin from Aspergillus terreus, an endophyte of Cestrum parqui, restoring their biosynthetic potency by Citrus limonum peel extracts

et al. 2023

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The metabolic potency of fungi as camptothecin producer elevates their prospective use as an industrial platform for commercial production, however, the loss of camptothecin productivity by fungi with the storage and subculturing are the major obstacle. Thus, screening for endophytic fungal isolates inhabiting ethnopharmacological plants with an obvious metabolic stability and sustainability for camptothecin biosynthesis could be one of the most feasible paradigms. Aspergillus terreus ON908494.1, an endophyte of Cestrum parqui was morphologically and molecularly verified, displaying the most potent camptothecin biosynthetic potency. The chemical identity of A. terreus camptothecin was confirmed from the HPLC, FTIR and LC–MS/MS analyses, gave the same molecular structure and mass fragmentation patterns of authentic one. The purified putative camptothecin displayed a strong anticancer activity towards HepG-2 and MCF-7 with IC50 values 0.96 and 1.4 µM, respectively, with no toxicity to OEC normal cells. As well as, the purified camptothecin displayed a significant antifungal activity towards fungal human pathogen Candida albicans, Aspergillus flavus, and A. parasiticus, ensuring the unique structural activity relationships of A. terreus camptothecin, as a powerful dually active anticancer and antimicrobial agent. The camptothecin productivity of A. terreus was maximized by bioprocessing with Plackett–Burman design, with an overall 1.5 folds increment (170.5 µg/L), comparing to control culture. So, the optimal medium components for maximum yield of camptothecin by A. terreus was acid why (2.0 mL/L), Diaion HP20 (2.0 g/L), Amberlite XAD (2.0 g/L), dextrin (5.0 g/L), glucose (10.0 g/L), salicylic acid (2.0 g/L), serine (4.0 g/L), cysteine (4.0 g/L) and glutamate (10.0 g/L), at pH 6 for 15 days incubation. By the 5th generation of A. terreus, the camptothecin yield was reduced by 60%, comparing to zero culture. Interestingly, the productivity of camptothecin by A. terreus has been completely restored and over increased (210 µg/L), comparing to the 3rd generation A. terreus (90 µg/L) upon addition of methanolic extracts of Citrus limonum peels, revealing the presence of some chemical signals that triggers the camptothecin biosynthetic machinery. The feasibility of complete restoring of camptothecin biosynthetic-machinery of A. terreus for stable and sustainable production of camptothecin, pave the way for using this fungal isolate as new platform for scaling-up the camptothecin production.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Production and bioprocessing of camptothecin from Aspergillus terreus, an endophyte of Cestrum parqui, restoring their biosynthetic potency by Citrus limonum peel extracts

et al. 2023

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“…Many scholars have studied endophytic fungi and their secondary metabolites in medicinal plants. El-Sayed et al optimized the biological process of Astragalus endophyte and tested its anticancer activity [ 1 ]. Amorim et al isolated antioxidant compounds from endophytic fungi of Luo Han Guo [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Endophytic Fungi and Secondary Metabolites of Rehmannia Glutinosa Based on Traditional Chinese Medicine Fingerprints

Geng

2022

Contrast Media & Molecular Imaging

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Research on the active components of medicinal plants has always been the focus of research, and research on the active components of medicinal plant endophytic fungi and their secondary metabolites has also attracted widespread attention. Endophytic fungi of medicinal plants are widely distributed and are ubiquitous in various biological groups in nature. Rehmannia glutinosa contains a variety of active ingredients, which are regarded as the top grade of Chinese medicinal materials. It is of certain significance to study endophytic fungi and their metabolites of Rehmannia glutinosa. In this paper, endophytic fungi and their secondary metabolites of Rehmannia glutinosa were studied using fingerprint technology, which initially understands the diversity of endophytic fungi in Rehmannia glutinosa. In this paper, the roots and leaves of Rehmannia glutinosa were used as experimental materials. The fungi were cultured in the medium, the fungi were isolated and purified by the tissue block method, the fungal growth of Rehmannia glutinosa in different parts was determined, and the types of endophytic fungi were identified by microscopic identification and fingerprinting. The isolated strains were tested for biological activity using oryza oryzae spores, and highly active strains were screened. Fermentation products of endophytic fungi were separated and purified by chromatography, and the structure of the compounds was identified by nuclear magnetic resonance spectroscopy. Through the above studies, the population structure of endophytic fungi of Rehmannia glutinosa was determined, 3 highly active strains were found, and the structures of 7 endophytic fungi metabolites were identified, of which 3 were newly discovered compounds.

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Progress on metabolites of Astragalus medicinal plants and a new factor affecting their formation: Biotransformation of endophytic fungi

Feng,

Cui

2024

Archiv der Pharmazie

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It is generally believed that the main influencing factors of plant metabolism are genetic and environmental factors. However, the transformation and catalysis of metabolic intermediates by endophytic fungi have become a new factor and resource attracting attention in recent years. There are over 2000 precious plant species in the Astragalus genus. In the past decade, at least 303 high‐value metabolites have been isolated from the Astragalus medicinal plants, including 124 saponins, 150 flavonoids, two alkaloids, six sterols, and over 20 other types of compounds. These medicinal plants contain abundant endophytic fungi with unique functions, and nearly 600 endophytic fungi with known identity have been detected, but only about 35 strains belonging to 13 genera have been isolated. Among them, at least four strains affiliated to Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae, and Camarosporium laburnicola have demonstrated the ability to biotransform four saponin compounds from the Astragalus genus, resulting in the production of 66 new compounds, which have significantly enhanced our understanding of the formation of metabolites in plants of the Astragalus genus. They provide a scientific basis for improving the cultivation quality of Astragalus plants through the modification of dominant fungal endophytes or reshaping the endophytic fungal community. Additionally, they open up new avenues for the discovery of specialized, green, efficient, and sustainable biotransformation pathways for complex pharmaceutical intermediates.

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Bioprocesses optimization and anticancer activity of camptothecin from Aspergillus flavus, an endophyte of in vitro cultured Astragalus fruticosus

Cited by 18 publications

References 58 publications

Production and bioprocessing of camptothecin from Aspergillus terreus, an endophyte of Cestrum parqui, restoring their biosynthetic potency by Citrus limonum peel extracts

Production and bioprocessing of camptothecin from Aspergillus terreus, an endophyte of Cestrum parqui, restoring their biosynthetic potency by Citrus limonum peel extracts

Endophytic Fungi and Secondary Metabolites of Rehmannia Glutinosa Based on Traditional Chinese Medicine Fingerprints

Progress on metabolites of Astragalus medicinal plants and a new factor affecting their formation: Biotransformation of endophytic fungi

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