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Optimization of submerged fermentation conditions for immunosuppressant mycophenolic acid production by Penicillium roqueforti isolated from blue-molded cheeses: enhanced production by ultraviolet and gamma irradiation

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Abstract

Mycophenolic acid (MPA) is a promising drug owing to its immunosuppressive and biological activities. In this study, two strains of Penicillium roqueforti designated as AG101 and LG109 were selected among several strains isolated from Roquefort cheese samples on the basis of their activity for MPA-producing ability. The appropriate fermentation conditions necessary for MPA biosynthesis by the two respective fungal strains were investigated. These conditions included selection of the cultivation medium, agitation rate, incubation temperature, fermentation time, pH value, inoculum size, and fermentation medium volume. Maximum MPA productivities were maintained when the fermentation process was carried out using a medium composed of (g l−1): Sucrose, 30; peptone, 5.0; KH2PO4, 1.0; MgSO4·7H2O, 0.5 and KCl, 0.5; pH 6.0, inoculated with an inoculum size of 6.0 % (v/v), and incubated at 25 °C for 10 days at 120 rpm. The potentiality of both P. roqueforti strains for further improvement of MPA production was applied by mutagenesis through exposure to irradiation by ultraviolet rays (UV, 254 nm) for different periods of time and gamma rays at various doses (KGy). The dry cell weight of both irradiated fungal strains showed a greater reduction when irradiated either with UV or gamma rays. However, the MPA yield of both strains was increased by 1.27–1.39 fold when irradiated with UV rays and by 2.11–2.33 fold when irradiated with gamma rays, as compared with the respective controls (non-irradiated cultures). These findings indicate the future possibility to reduce the cost of producing fermentation-based drugs.

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Acknowledgments

We thank the staff members of Central Laboratories of Isotopes Applications Division, Nuclear Research Center, Atomic Energy Authority, Inshas for excellent technical assistance in performing HPLC analysis. This work was supported in part by the Nuclear Research Center, Atomic Energy Authority, Inshas, Egypt.

Conflict of interest

The authors declare that they have no conflicts of interest concerning this article.

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Authors and Affiliations

  1. Department of Botany and Microbiology, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt

    Ahmed A. Ismaiel & El-Sayed R. El-Sayed

  2. Plant Research Department, Nuclear Research Center, Atomic Energy Authority, Inshas, Egypt

    Ashraf S. Ahmed & El-Sayed R. El-Sayed

Authors
  1. Ahmed A. Ismaiel
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  2. Ashraf S. Ahmed
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  3. El-Sayed R. El-Sayed
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Correspondence to Ahmed A. Ismaiel.

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11274_2014_1685_MOESM1_ESM.tif

Supplementary Fig. S1. Effect of initial pH of broth medium adjusted by 1 N of both HCl and NaOH (a and b) or citrate phosphate buffer (c and d) on growth and production of MPA by AG101 (a and c) and LG109 (b and d) strain. Cultures were carried out at 25 °C and 120 rpm for 10 days in CDYE broth containing an inoculum size of 1 ml/50 ml medium. Data are shown as the mean ± SD of triplicate measurements from two independent experiments. (TIFF 2390 kb)

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Ismaiel, A.A., Ahmed, A.S. & El-Sayed, ES.R. Optimization of submerged fermentation conditions for immunosuppressant mycophenolic acid production by Penicillium roqueforti isolated from blue-molded cheeses: enhanced production by ultraviolet and gamma irradiation. World J Microbiol Biotechnol 30, 2625–2638 (2014). https://doi.org/10.1007/s11274-014-1685-1

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  • DOI: https://doi.org/10.1007/s11274-014-1685-1

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