Response Surface Methodology for Optimization of the Erythromycin Production by Fed-Batch Fermentation Using an Inexpensive Biological Nitrogen Source

A novel source of biological nitrogen produced by multi-strain fermentation was developed for erythromycin production. The nitrogen composition of corn steep liquor, biological nitrogen and soybean flour was optimized by using Response surface methodology (RSM) firstly. A Box-Behnken design was used to estimate the optimum nitrogen composition for the production of erythromycin as follows: corn steep liquor: gamma = 5.1 g L-1, biological nitrogen gamma = 5.96 g L-1 and soybean flour gamma = 24.17 g Based on the optimum nitrogen source, the constant glucose fed-batch and pH control fed-batch strategies were used to further optimize the erythromycin production in 50 L-1 stirred bioreactor, respectively. It was found that pH control could serve as an effective control strategy for erythromycin production, and the maximum erythromycin production was 8528 U mL(-1) at 190 h. This work demonstrates that the new medium formulation based on a cheap nitrogen source, biological nitrogen, is a potential alternative for economic erythromycin production on a large scale.