Optimal feeding strategy of Cephalosporin C fermentation

Abstract

Cephalosporin C is a β-lactam type of antibiotic produced from the fungus Acremonium chrysogenum through fermentation process, either by batch or fed-batch mode. Cephalosporin represents the bulk majority of antibiotic production due to its enhanced antibacterial spectrum against gram positive and gram negative bacterial strains relating to diseases and infections in the skin, respiratory system, and urinary tract. In the production process, it is crucial to maximize the yield of antibiotic produced, since the major costs of production come from the fermentation and recovery of the antibiotic. To address this issue, an effective feeding strategy of the culture producing the target antibiotic is very important to achieve high yield and avoid undesired production of other metabolites, which reduce the yield of desired metabolite. The latter can add extra cost to recovery and purification of the desired metabolite. This paper presents an optimal strategy for the fed-batch fermentation process producing Cephalosporin C (CPC) from the fungus A. chrysogenum by optimization of the substrate feeding flow rate. The preferred substrates are glucose and sucrose as the fungus possesses diauxic behaviour in the presence of the two carbon sources. It is shown that a two-step fed-batch feeding of glucose results in a significantly higher antibiotic production than a batch mode or single-step fed-batch feeding strategy.