Bioreactor studies of production of mycophenolic acid by Penicillium brevicompactum

Abstract

Batch and fed-batch fermentation processes for the production of mycophenolic acid (MPA) were optimized and compared. MPA was produced using the microfungus Penicillium brevicompactum. Different feeding strategies were assessed in fed-batch fermentations in a 14 L stirred bioreactor. A batch fermentation attained a maximum total (extracellular and intracellular) MPA concentration of 1.26 g/L after 288 h. The best fed-batch operation involving a constant-rate feeding of sorbitol (a feeding rate = 0.07 g/min, from 48 h to 240 h) and the pH controlled at 6, enhanced the total maximum MPA concentration to 3.26 g/L. The yield of MPA on substrate was 0.028 g/g, some 47% greater than in the aforementioned batch culture. The fermentation was highly aerobic. The fermentation temperature was 25 °C. Glucose could be used as an effective substrate instead of sorbitol, but the final total MPA concentration in a fed-batch fermentation using glucose was reduced to 2.72 g/L.