Optimization And Metabolic Regulation Of Kitasamycin Component

The kitasmycin is widely used in pharmaceutical and veterinary industry. Kitasmycin is a family of multicomponent antibiotic, which is produced by Streptomyces kitasatoensis and mainly contains A5, A4, A1 and A3. There are problems that low kitasamycin titer and poor kitasamycin component in the fermentation process. Here in, we carried out a series of studies on above problems.In this research, the optimized seed age was 26 h in shaker fermentation, which decreased the kitasamycin Ai content. The optimum age for second seed was 18 h, and the inoculum concentration was 10% in 15 L fermentor.Adding 1.2%glycerol to the shaker fermentation medium, the titer was increased 47% and the content of A5 was increased 17.4% comparing to the control. The lipase activity was higher by adding glycerol, making soybean oil decomposed quickly and producing more propionic acid, which promoted the biosynthesis of kitasamycinan. The low concentration of acetic acid, which might weaken the acetylation at C-3 of lactone, reduced the concentration of A4 component and increased the concentration of A5 component.Different sources of soybean meal hardly affected the fermentation of kitasamycin. There were higher A1 content and lower A5 content with yeast extract and corn steep liquid in fermentation medium, which might be caused by high concentration of leucine and low concentration of valine in yeast extract and corn steep liquid. Using 0.38%of ammonium sulfate to replace silk fibroin powder in fermentation medium, the final titer of kitasamycin reached to 10186 U/mL, which was 20.3% higher than the control, while the components were not affected.When 0.5 g/L SDS was added in the fermentation medium, the titer of kitasamycin was increased by 52.7% and A5 content was increased 20% comparing to the control. It was found that the oil consumption rate and lipase activity were improved, and utilization of oil components by Streptomyces kitasatoensis was changed. Linoleic acid was mainly used after adding SDS, while oleic acid was mainly used in the control. The surface between oil and water was increased by adding SDS, which might make double bonds of linoleic acid to break easily by strong oxidizing substances in fermentation broth. As a result, the content of butyric acid was high, which promoted the synthesis of kitasamycin A5 component.