Research On Erythromycin Biosynthesis And Components Optimization

Erythromycin(Er) is a typical macrolide antibiotics including Erythromycin A, B, C, D, E, F. Among all of them, Erythromycin A has the most effective antibacterial activity and is the target component.Different Erythromycin production strains have different fermentation characteristics. Through study on the fermentation process we can understand the fermentation characteristics clearly and control fermentation effectively. Metal ions play an important part in the biosynthesis of erythromycin, which can be used as auxiliary factors related to erythromycin biosynthesis enzyme. Metal ions can also promote the formation of erythromycin cellular structure, and then improve the erythromycin production efficiency. Oxygen carrier can greatly improve the oxygen status during fermentation process. Combined with the methylation reagent choline chloride surfactant can enhance methylation and hydroxylation of erythromycin D.The fermentation process of two strains is is studied in this paper. Using stain HA to transform strain HD’s fermentation broth, results showed that HA (cultured for96h) can convert HD fermentation broth (cultured for144h) mostly in72h, the relative percentage of erythromycin A increased from78%to86.6%. Considering the use of Oxygen carrier could cause foam formation in fermentation tank, bubble forming was studied. The final titer improved from8433u/ml (control) to9100u/ml, the relative percentage of erythromycin A improved from83.6%to90.91%, erythromycin B decreased from7.38%to2.59%. Supplementing CoCl2, ZnCl2and Na2MoO4during fermentation process could improve the final titer from8433U/ml to11858U/ml, the relative percentage of erythromycin A increased from83.6%to88.98%.At the same time, gene expression of eryK and eryG was studied using eryAⅢ as control. Results revealed that the gene expression of eryK and eryK/eryG had a relatively close relationship with the chemical titer and components of erythromycin. In addition of metal ions and tween80can improve gene expression of eryK and eryG. To some extent, this may explain the reason of increasing of erythromycin titer and good components.