Evaluation of mycophenolic acid production by Penicillium brevicompactum MUCL 19011 in batch and continuous submerged cultures

Mycophenolic acid (MPA) is a secondary metabolite produced by Penicillium brevicompactum, which has antibiotic and immunosuppressive properties. In this study, production of MPA by P. brevicompactum MUCL 19011 in shake flask and a 2 L bench-scale stirred tank bioreactor under batch and continuous culture conditions was evaluated. The maximum concentration of MPA, its yield and rate of production in continuous culture were 1.46 g L−1, 29 mg g−1 glucose and 6.8 mg L−1 h−1, respectively. Growth kinetics in batch culture was investigated with five models of Monod, Moser, Verhulst, Contois and Exponential. The compatibility of the experimental data fitted well with the Contois model and the regression value was 0.98. The maximum specific growth rate and saturation constant were 0.07 h−1 and 0.61 g L−1, respectively. Glucose, biomass and MPA concentration profiles were evaluated during the course of fermentation. Under steady-state conditions, glucose consumption, biomass formation and MPA production fluxes were 9.2, 22.35 and 0.194 mmol L−1 h−1, respectively. In batch culture, enzymatically hydrolyzed casein and glycine increased MPA production by 165 and 112%, respectively.