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Production, bioprocess optimization and γ-irradiation of Penicillium polonicum, as a new Taxol producing endophyte from Ginko biloba

ABSTRACT: Highlights • Penicillium polonicum, an endophyte of Ginkgo biloba, is a potent Taxol producer.• Taxol of P. polonicum has a strong anticancer effect against HEPG2 and MCF7.• The Taxol yield by P. polonicum was increased by 4.5 folds upon optimization with response surface methodology. Twenty-eight fungal endophytes were recovered from the different parts of Ginkgo biloba and screened for their Taxol producing potency. Among these isolates, Penicillium polonicum AUMC14487 was reported as the potent Taxol producer (90.53 μg/l). The chemical identity of the extracted Taxol was verified from the TLC, HPLC, NMR, EDX, and FTIR analyses. The extracted Taxol displayed a strong antiproliferative activity against HEPG2 (IC50 4.06 μM) and MCF7 (IC50 6.07 μM). The yield of Taxol by P. polonicum was optimized by nutritional optimization with the Response Surface Methodology (RSM) using Plackett-Burman and Central Composite Designs. In addition to nutritional optimization, the effect of γ-irradiation of the spores of P. polonicum on its Taxol producing potency was evaluated. The yield of Taxol by P. polonicum was increased via nutritional optimization by response surface methodology with Plackett-Burman and FCCD designs, and γ-irradiation by about 4.5 folds, comparing to the control culture. The yield of Taxol was increased by about 1.2 folds (401.2 μg/l) by γ -irradiation of the isolates at 0.5−0.75 kGy, comparing to the control cultures (332.2 μg/l). The highest Taxol yield was obtained by growing P. polonicum on modified Czapek’s- Dox medium (sucrose 40.0 g/l, malt extract 20.0 g/l, peptone 2.0 g/l, K2PO4 2.0 g/l, KCl 1.0 g/l, NaNO3 2.0 g/l, MgSO4. 5H2O 1.0 g/l) of pH 7.0 at 30.0 °C for 7.0 days. From the FCCD design, sucrose, malt extract and incubation time being the highest significant variables medium components affecting the Taxol production by P. polonicum.

SUBMITTER: Abdel-Fatah S

PROVIDER: S-EPMC8120861 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Taxol production by fungi is one of the promising alternative approaches, regarding to the natural and semisynthetic sources; however, the lower yield and rapid loss of Taxol productivity by fungi are the major challenges that halt their further industrial implementation. Thus, searching for fungal isolates with affordable Taxol-production stability, in addition to enhance its anticancer activity via conjugation with gold nanoparticles, is the main objectives of this study. Twenty-four endophytic fungal isolates were recovered from the barks, twigs, and leaves of jojoba plant, among these fungi, Aspergillus flavus MW485934.1 was the most potent Taxol producer (88.6 µg/l). The chemical identity of the extracted Taxol of A. flavus was verified by the TLC, HPLC, HNMR, and FTIR analyses. The yield of Taxol produced by A. flavus was optimized by the response surface methodology (RSM) using Plackett-Burman (PBD) and faced central composite designs (FCCD). The yield of Taxol by A. flavus was increased by about 3.2 folds comparing to the control cultures (from 96.5 into 302.7 µg/l). The highest Taxol yield by was obtained growing A. flavus on a modified malt extract medium (g/l) (malt extract 20.0, peptone 2.0, sucrose 20.0, soytone 2.0, cysteine 0.5, glutamine 0.5, and beef extract 1.0 adjusted to pH 6.0) and incubated at 30 °C for 16 days. From the FCCD design, the significant variables affecting Taxol production by A. flavus were cysteine, pH, and incubation time. Upon A. flavus γ-irradiation at 1.0 kGy, the Taxol yield was increased by about 1.25 fold (375.9 µg/l). To boost its anticancer activity, the purified Taxol was conjugated with gold nanoparticles (AuNPs) mediated by γ-rays irradiation (0.5 kGy), and the physicochemical properties of Taxol-AuNPs composite were evaluated by UV-Vis, DLS, XRD, and TEM analyses. The IC50 values of the native-Taxol and Taxol-AuNPs conjugates towards HEPG-2 cells were 4.06 and 2.1 µg/ml, while the IC50 values against MCF-7 were 6.07 and 3.3 µg/ml, respectively. Thus, the anticancer activity of Taxol-AuNPs composite was increased by 2 folds comparing to the native Taxol towards HEPG-2 and MCF-7 cell lines. Also, the antimicrobial activity of Taxol against the multidrug resistant bacteria was dramatically increased upon conjugation with AuNPs comparing to authentic AuNPs and Taxol, ensuring the higher solubility, targetability, and efficiency of Taxol upon AuNPs conjugation.

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Production, bioprocess optimization and γ-irradiation of Penicillium polonicum, as a new Taxol producing endophyte from Ginko biloba

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