AimsDifferent entrapment matrices were screened to immobilize two strains of Penicillium roqueforti (AG101 and LG109) for more effective production of mycophenolic acid (MPA). Further improvement in the MPA productivity from immobilization of spores and mycelia was adopted by UV and gamma irradiation. Methods and ResultsPenicillium roqueforti strains were immobilized in different entrapping carriers and used for MPA production in shake flask cultures. Maximum MPA production was achieved on using an alginate concentration of 30% (w/v) and a mycelial fresh weight of 10% (w/v). MPA produced by alginate-immobilized spores and mycelia was almost double in comparison to the free system. The MPA-producing ability of immobilized AG101 and LG109 strain was significantly enhanced by mutagenesis through irradiation by UV (254nm) for 120 and 90min, respectively and gamma rays at 075KGy. The feasibility of MPA production in a semi-continuous form by immobilized cells as affected by irradiation was adopted. ConclusionsMPA production by immobilized spores and mycelia was more intensified by UV and gamma irradiation. Moreover, the immobilized cell culture was superior to free-cell culture. Significance and Impact of the StudyThese findings indicate the future possibility to reduce the cost of producing fermentation-based drugs.