Dissertation > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Antibiotics manufacture > Macrocyclic lactone family of antibiotics

Erythromycin Fermentation Process Regulation and Optimization by Saccharopolyspora Erythraea

Author ChangXianTong
Tutor ZhuangYingPing
School East China University of Science and Technology
Course Fermentation Engineering
Keywords Erythromycin Nitrogen regulation Recombinant strain Fermentation Processoptimization
CLC TQ465.5
Type Master's thesis
Year 2013
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Erythromycin is one of the macrolide antibiotics produced by Saccharopolyspora erythraea. As its semi-synthetically modified derivatives are developed and used in the clinical, the demand for erythromycin is increasing tremendously and a rigorous standard of erythromycin production is required. In this paper, we optimized the fermentation process of erythromycin by industrial erythromycin producer strain Q8and recombinant strain ZL1004to improve the yield and quality of erythromycin.Based on the anlaysis of the content of amino acids in the organic nitrogen source for erythromycin fermentation, a new complex nitrogen source was designed, in which we realized the rational combination of amino acids and the optimization of quality of protein in nitrogen source. It was found that using optimized nitrogen source in the medium was beneficial for the process of erythromycin fermentation, the production of erythromycin was22.5%higher than that of control in shake flask experiment. Further investigation was carried out in50L fermentor, in comparison with control the active constituent EryA increased9.4%and moreover the impure components EryB and EryC decreased17.9%and33.1%respectively.The results in25m3fermentor showed that a new industrial feather peptone is beneficial for the process and production of erythromycin fermentation by ZL1004,which is proved in50L fermentor in our previous work. But there are two problems to be sloved in the process,high viscosity and mass transfer difficulty. To slove the problems mentioned above,we lowered the phosphorus content of the organic nitrogen for erythromycin production by using defatted soybean instead of part of soybean. After the substitution in50L fermentor, the viscosity of fermentation process was reduced greatly and the active constituent EryA increased11.2%in comparison of control.Based on the comparison of the fermentation process in372m3fermentor between ZL1004and Q8,We optimized the fermentation process of ZL1004by means of improving the quality of secondary seed and adjusting the fermention medium,culture temperature and glucose feeding strategy. After optimization of fermentation process, the active constituent EryA reached7485μg/ml,which is17.2%high than control.

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