Strain improvement and immobilization technique for enhanced production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima

El‐Sayed, El‐Sayed R.; Ahmed, Ashraf S.; Hassan, Ismail A.; Ismaiel, Ahmed A.; El-Din, Al-Zahraa A. Karam

doi:10.1007/s00253-019-10129-1

Cited by 44 publications

(22 citation statements)

References 41 publications

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“…At this dose of irradiation, the recorded digoxin concentration was significantly intensified to 10Á65 AE 0Á33 mg l À1 which was approximately fivefold as compared by non-irradiated control culture. In partial accordance with these results, production of the anticancer drug paclitaxel by A. fumigatus and A. tenuissima irradiated at 750 Gy was twice as compared by the nonirradiated controls (El-Sayed et al 2019b, 2019c, 2019b, 2019c. Moreover, irradiation of two Penicillium roqueforti strains at the same dose (750 Gy) significantly enhanced the production of the immunosuppressant of mycophenolic acid (Ismaiel et al 2014(Ismaiel et al , 2015El-Sayed et al 2019a).…”

Section: Elicitorsupporting

confidence: 74%

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

2019

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Aims Different endophytic fungi were isolated and screened for their digoxin‐producing ability. Strain improvement and different culture conditions were studied for more effective production of digoxin. Methods and Results Among the isolated fungi, an isolate produced digoxin in a concentration of 2·07 mg l−1. The digoxin‐producing fungal isolate was identified as Epicoccum nigrum Link according to the morphological features and phylogenetic analyses. The potentiality of the fungal strain for production enhancement of digoxin was performed by gamma radiation mutagenesis. Gamma irradiation dose of 1000 Gy intensified the digoxin yield by five‐fold. Using this dose, a stable mutant strain with improved digoxin productivity was isolated and the stability for digoxin production was followed up across four successive generations. In the effort to increase digoxin magnitude, selection of the proper cultivation medium, addition of some elicitors to the most proper medium and several physical fermentation conditions were tested. Fermentation process carried out in malt extract autolysate medium (pH 6·5) supplemented by methyl jasmonate and inoculated with 2 ml of 6‐day‐old culture and incubated at 25°C for 10 days stimulated the highest production of digoxin to attain 50·14 mg l−1. Moreover, cytotoxicity of digoxin separated from the fungal culture was tested against five different cancer cell lines. Based on the MTT assay, digoxin inhibited the proliferation of the five different cancer cell lines and the recorded 50% inhibitory concentration ranged from 10·76 to 35·14 μg ml−1. Conclusions This is the first report on the production and enhancement of digoxin using fungal fermentation as a new and alternate source with high productivity. Significance and Impact of the Study These findings offer new and alternate sources with excellent biotechnological potential for digoxin production by fungal fermentation. Moreover, digoxin proved to be a promising anticancer agent whose anticancer potential should be assessed in prospective cancer therapy.

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Section: Elicitorsupporting

confidence: 74%

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

2019

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“…Among the fungal populations, endophytic fungi are a group of fungi which spend their whole or part of their lifecycle colonizing the inside of healthy tissues of the host plants, typically causing no apparent symptoms of disease (Ismaiel et al ). Endophytic fungi represent an untapped pool of valuable metabolites (El‐Sayed et al , 2019b; Zaki et al ). Moreover, they are metabolically more active than their free counterparts; so, they are recognized as sources of novel metabolites with potential application in agriculture, medicine and food industry (El‐Sayed et al 2019c, 2020c).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of zinc oxide nanoparticles with antimicrobial, anticancer, antioxidant and photocatalytic activities by the endophytic Alternaria tenuissima

2020

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Aims Zinc oxide nanoparticles (ZnONPs) were successfully synthesized using the culture filtrate of the endophytic fungus Alternaria tenuissima as a rapid, eco‐friendly and cost‐effective method. Methods and Results The rapid synthesis of ZnONPs was completed after 20 min as confirmed by UV–Vis spectroscopy. The synthesized ZnONPs showed a single‐phase crystalline structure. Dynamic light scattering analysis showed that the synthesized ZnONPs were monodispersed and the recorded polydispersity index value was 0·311. Zeta potential value of –23·92 mV indicated the high stability of ZnONPs. Transmission electron microscope revealed the spherical shape and the mean particle size was 15.45 nm. Functional groups present in the prepared samples of ZnONPs were confirmed by Fourier transform infrared spectroscopy. Additionally, the biological activities of in vitro antimicrobial, anticancer, antioxidant as well as the photocatalytic activities were evaluated. ZnONPs showed broad spectrum of antimicrobial potential against all the tested plant and human pathogens. Based on the MTT assay, ZnONPs inhibited the proliferation of normal human melanocytes, human breast and liver cancer cell lines with IC50 concentrations of 55·76, 18·02 and 16·87 µg ml−1. ZnONPs exhibited promising antioxidant potential with 50% inhibitory concentration of 102·13 µg ml−1. Moreover, ZnONPs showed efficient degradation of methylene blue dye. Conclusions The synthesized ZnONPs showed promising activities that can be better explored in the near future for many medical, agricultural and industrial applications. Significance and Impact of the Study This study suggests a new and alternate approach with the excellent biotechnological potentiality for the production of ZnONPs which could open up the way for the industrial manufacture of nanoparticles using microbial platforms.

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“…In literature, several reports recommended both types of radiation in the production enhancement of many fungal metabolites (Paster et al ; Thaker et al ; Chopra ; Ismaiel et al , ; El‐Sayed et al . ,b,c,d; El‐Sayed et al ,b). Regarding the effect of irradiation (UV or gamma) on the fungal growth, a significant decrease in the recorded glucosamine concentrations was observed when compared with their respective control (nonirradiated culture).…”

Section: Discussionmentioning

confidence: 99%

Agro‐industrial wastes for production of paclitaxel by irradiated Aspergillus fumigatus under solid‐state fermentation

2020

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Aims: Paclitaxel is the most profitable drug ever developed in cancer chemotherapy; however, the yield of paclitaxel from microbial platforms is still far from the commercial purpose. Thus, this study was conducted to explore the possibility of solid-state fermentation (SSF) for production of paclitaxel by fungal fermentation. Methods and Results: Different agro-industrial wastes were screened as solid substrates for production of paclitaxel by the endophytic Aspergillus fumigatus TXD105 under SSF. Sugarcane bagasse followed by wheat bran, and rice bran were the most suitable substrates for maximum production of paclitaxel. In the effort to increase the paclitaxel production, selection of the most proper moistening agent that supports the production of paclitaxel by the fungal strain was investigated. The effect of varying inoculum concentrations on the production of paclitaxel was also studied. Moreover, optimization of SSF conditions (moisture level, substrate concentrations and nutrients concentration) was adopted using response surface methodology. SSF carried out under the optimum conditions of 20 g sugarcane bagasse, twofold nutrients concentration of the MM1D broth, 80% moisture level and inoculum concentration of 10 7 spores per ml intensified the paclitaxel concentration to 145Á61 mg kg À1 which represents a 10-fold increase. The production of paclitaxel by the fungal strain was further improved via exposure to UV and gamma radiation at specific doses. The paclitaxel concentrations were intensified following UV and gamma radiation to 209Á91 and 351Á82 mg kg À1 . Conclusions: This is the first report on the production of paclitaxel using agro-industrial wastes as cheap source that may contribute in lowering the cost of producing paclitaxel. Significance and Impact of the Study: These findings offer new and alternate sources with excellent biotechnological potential for paclitaxel production by fungal fermentation.

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Strain improvement and immobilization technique for enhanced production of the anticancer drug paclitaxel by Aspergillus fumigatus and Alternaria tenuissima

Cited by 44 publications

References 41 publications

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

A novel source of the cardiac glycoside digoxin from the endophytic fungus Epicoccum nigrum : isolation, characterization, production enhancement by gamma irradiation mutagenesis and anticancer activity evaluation

Biosynthesis of zinc oxide nanoparticles with antimicrobial, anticancer, antioxidant and photocatalytic activities by the endophytic Alternaria tenuissima

Agro‐industrial wastes for production of paclitaxel by irradiated Aspergillus fumigatus under solid‐state fermentation

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