Scaling up production of cephalosporin C by Acremonium chrysogenum W42-I in a fermenter using submerged fermentation

Abstract

Cephalosporins presently stand as the most extensively utilized antibiotic in clinical settings. Acremonium (A.) chrysogenum is the main strain used in the manufacturing of cephalosporin C (CPC), which offers distinct advantages, including a wide-ranging antibacterial spectrum and powerful antibacterial efficacy. Our study aimed to determine the optimal conditions for scaling up the production of CPC from A. chrysogenum W42-I starting with the optimized conditions on the shake flask level obtained from our previous study and utilizing the optimized media (CPC2). The results indicated that an inoculum size equivalent to 1% v/v, aeration at 1 vvm, and an agitation rate of 400 rpm, with controlled pH at 4, were the most favorable conditions for the CPC production using a laboratory fermentor (14 L). The concentration of generated CPC was assessed using two standard curves obtained from agar well diffusion and high-performance liquid chromatography (HPLC). These optimized conditions resulted in a production of 399.52 µg/mL showing a significant increase of approximately 3.4 folds when compared to the unoptimized fermentation run. In conclusion, our findings demonstrated a more favorable time course for CPC production in the fermentor compared to that in the shake flask. Notably, there was a two-fold increase in production within the first three days. Fortunately, the fermentor achieved a noteworthy increase in output, generating 1.598 gm of the CPC within 4 L.

Key points

Cephalosporin C production was successfully scaled up and optimized using a 14 L fermentor resulting in about 3.4 folds as compared to the unoptimized condition.

Using the lab fermentor (14 L), a two-fold increase of CPC was attained in the first three days as compared to that of the shake flask.

Using the lab fermentor (14 L), the fermentor achieved a noteworthy increase in output, generating 1.598 gm of the CPC/4 L fermentation medium.