Vancomycin Fermentation Optimization

Production of the glycopeptide antibotic vancomycin by Amycolatopsis orientalis V-0704 provided by North China Pharmaceutical Huasheng CO. LTD was investigated in this study. In the flask culture a optimized complex medium was obtained using the response surface methodology, which contained maltose 20 g/L, corn oil 15 g/L, glucose 15 g/L as the carbon sources and yeast powder 0.568 g/L, pharmamedia 6.98 g/L, soybean flour 23.3 g/L as the nitrogen sources. The vacomycin titre is 4113U/ml which is as twice as that using the original medium containing soybean flour 36 g/L, maltose 150 g/L, glucose 15 g/L. The same mathod was used to optimize the supplementation concentrations of trace metal Co2+ and Mo6+. After that the antibiotic titre of vancomycin was increasd by 17% further and the average vancomycin titre was increased to 4946U/ml.In the design of fed-batch fermentation process in an 100 L bioreactor, the multi-scale methodology was used to determine the glucose feeding strategy. Additionally the feeding strategy of the precusor NaAC, trace metals was determined according to the trend of the DO and pH value in the course. The vancomycin titre 8500 U/ml was obtained at the 120 h, indicating a 100% increase as that in the original batch fermentation process.Finally a competitive network was designed to classify the physical phase of the cells and a 2-hidden layer neural network was used to depict the non-linear fermentation process.