Comparative Study for the Production of Mycophenolic Acid using Penicillium brevicompactum in Batch, Fed-batch and Continuous Fermentation Process

Abstract

Mycophenolic acid (MPA) is, due to its immunosuppressive and biological activities, a potential compound. It is the secondary metabolite produced in submerged cultivation by the microfungus Penicillium brevicompactum. Batch, fed-batch, and continuous mode of cultivation for mycophenolic acid production were performed and compared in the current work. To increase productivity, mycophenolic acid production was studied in batch, fed-batch, and continuous bioreactors. These experiments were conducted with a 2.5 L working volume in a 3.7 L continuous stirred tank bioreactor. In all cases, operating conditions such as temperature, pH, agitation, and aeration, 28 °C, 5.5, 200 rpm, and 2 vvm, respectively, were the same. In fed-batch fermentation, the MPA concentration obtained was 1.91 g/L higher than the value obtained in batch culture, 1.55 g/L, while in continuous fermentation, 1.67 g/L was obtained. The mycophenolic acid productivity obtained in the continuous fermentation process was 0.025 g/L/h, which was maximum MPA productivity, compared to 0.007 g/L/h in the fed-batch fermentation process and 0.006 g/L/h in the batch fermentation process. The impact of substrate inhibition on the product formation can effectively bring down by continuous fermentation processes. The MPA productivity was increased in continuous fermentation relative to batch and fed-batch processing. The finding indicates that continuous culture of Penicillium brevicompactum is a promising strategy for the synthesis of mycophenolic acid.