Process for the production of mycophenolic acid

摘要

According to the present invention mycophenolic acid (MPA) is produced in submerged fermentation, by using mutant of Penicillium brevicompactum ATCC16024 (IMI 17456) in aerobic conditions. The process of the invention consists in two or more fermentations in sequence, being one or more seed fermentations and one production fermentation. In the production fermentation a shift in temperature and/or pH is made at certain biomass concentration and accordingly MPA concentrations of 3.4g/L in the fed-batch reactor and 2.6g/L in the batch reactor were attained. The inoculum percentage was optimized to maximize the final MPA concentration. Additionally, the process according to the invention follows a biomass separation method, which comprises a chromatographic step using an adsorption resin. After the elution using an organic solvent, a precipitation step is performed using chilled water at low pH, the precipitate is then centrifuged and dried in an oven. The MPA purity attained is approximately 98%. The process according to the present invention has the advantages of high productivity, of using simple processes and was designed baring in mind the scalability of the entire process to a full production scale. Pilot scale was used to test the scale-up parameters. A fermentation with working volume of 300L was used.