Application of oxygen uptake rate and response surface methodology for erythromycin production by Saccharopolyspora erythraea |
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Authors: | Xiang Zou Hai-feng Hang Chang-fa Chen Ju Chu Ying-ping Zhuang Si-liang Zhang |
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Institution: | (1) State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, P. O. Box 329, 130 Meilong Road, 200237 Shanghai, People’s Republic of China;(2) School of Pharmaceutical Sciences, Southwest University, 400715 Chongqing, People’s Republic of China |
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Abstract: | A process for efficient production of erythromycin by Saccharopolyspora erythraea using statistical designs and feeding strategy was developed. The critical nutrient components were selected in accordance
with fractional factorial design and were further optimized via response surface methodology. Three significant components
(ZnSO4, citric acid threonine) were identified for the optimization study. The optimum levels of these significant variables were
determined with Box–Behnken design, which were ZnSO4 0.039 g/l, citric acid 0.24 g/l and threonine 0.42 g/l, respectively. A novel feeding strategy based on oxygen uptake rate
(OUR) measurement was developed successfully to increase the flux of erythromycin biosynthesis, in which the optimized nutrient
components was fed in the 50 l stirred bioreactor when OUR began to decline at 46 h. The maximum erythromycin production reached
10,622 U/ml, which was 11.7% higher than the control in the same cultivation conditions. It was the first report to integrate
physiological parameter OUR and statistical methods to optimize erythromycin production. |
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Keywords: | Bioreactors Erythromycin Fed-batch culture Physiology Process integration Response surface methodology |
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