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

X. Zou, C. Chen, H. Hang, J. Chu, Y. Zhuang and S. Zhang

Abstract
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: γ = 5.1 g L–1, biological nitrogen γ = 5.96 g L–1 and soybean flour γ = 24.17 g L–1. 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 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.

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Keywords
Biological nitrogen, erythromycin production, fed-batch strategy, Medium optimization, response surface methodology, Saccharopolyspora erythraea