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

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.

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

“…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 non‐irradiated controls (El‐Sayed et al , ). 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 , ; El‐Sayed et al ).…”

Identification and Functional Analysis of the Mycophenolic Acid Gene Cluster of Penicillium roqueforti

“…On the other hand, recent experiments suggest that P . roqueforti strains submitted to random-mutagenesis by UV and gamma irradiation may be suitable for the commercial production of MPA [ 15 ]. Therefore, knowledge of the molecular basis underlying to the biosynthesis of MPA in P .…”

Production of mycophenolic acid by Penicillium brevicompactum—A comparison of two methods of optimization

“…Mycophenolic acid (6-(4-hydroxy-6-methoxy-7-methyl-3oxophthalanyl)-4-methyl-4-hexenic acid, C 17 H 20 O 6 , MPA) is a fungal secondary metabolite that was first isolated in 1893 as an antibiotic against Bacillus anthracis [1] , [2] . MPA is produced by many Penicillium species [3] , [4] , [5] , [6] , [7] , [8] as well as other fungi [6] , [9] . MPA and its derivatives are commercially used as frontline immunosuppressive agents to prevent rejection of transplant organs [10] , [11] , [12] .…”