الفهرس 
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Abstract
In this study comparative findings for the production of the immunosuppressant MPA by two strains of Penicillium roqueforti (AG101 and LG109) under fermentation by submerged, solid state and immobilized-grown cultures were demonstrated. UV and gamma irradiation was applied to each fermentation system to enhance the MPA production process. Optimization studies of submerged fermentation conditions showed that medium formulation of sucrose (3.0%), peptone (0.5%), KH2PO4 (0.1%), MgSO4.7H2O (0.05%), and KCl (0.05%) favored the highest MPA productivity when the favorable conditions were established at pH 6.0, temperature 25ºC, fermentation time 10 days, inoculum 3 ml/50 ml medium and agitation rate 120 rpm. A greater increase in MPA concentration by 1.39 and 1.27 times was resulted following irradiating the spores of AG101 and LG109 cultures, respectively to UV light. The MPA-producing ability of both strains was more intensified to 2.33 and 2.11 fold, respectively; as compared to non-irradiated cultures when irradiated with 0.75 KGy gamma rays. Production of MPA under SSF conditions showed a distinct advantage over submerged fermentation for the production of MPA because of its increased yield of MPA by the two strains of P. roqueforti and the maximum rates of MPA productivities were achieved on using sugarcane bagasse (at a moisture content of 70%) as solid substrate. Applying SSMB as a moistening agent promoted a greater increase in MPA concentration than applying MSS as a moistening agent. Gamma irradiation was found to be more effective than UV irradiation in MPA production by solid-state cultures grown on sugarcane bagasse. Application of the immobilization technique revealed that calcium alginate beads were found to be the most proper carrier for MPA production process by both immobilized spores and mycelia of the two fungal strains. The best alginate concentration was found to be 3% (w/v). Immobilized mycelia achieved greater MPA production than immobilized spores and the highest concentration was achieved on using mycelium fresh weight at 10% (w/v).
MPA production by immobilized spores and mycelia was more intensified by UV and gamma irradiation. This study suggested the production of MPA in a semi-continuous form using the advantage of the repeated use availability of the cell immobilization techniques. The total MPA concentration obtained from immobilization of gamma-irradiated cells along 4 different cycles of fermentation was 38.54±0.83 mg l-1 and 35.16± 0.74 mg l-1 by AG101 and LG109 strain, respectively; which was about 1.36 times of UV-irradiated immobilized cells of both fungal strains. These results also concluded the superiority of the immobilized cell culture to free cell culture. Further work should focus on identifying the hereditary stability and the mechanism by which UV and gamma irradiation help cells to produce more MPA.