Production of Pimaricin by streptomyces natalensis in submerged culture

In this project, the production of the antifungal antibiotic, Pimaricin, by Streptomyces natalensis was investigated with a view to developing an Industrial fermentation process. A suitable medium was developed to produce dispersed growth in submerged culture, which was desirable for optimum antibiotic production. A spectrophotometric assay was successfully developed to rapidly determine the concentration of the antibiotic in culture supernates. Results from this assay were shown to be in agreement with the traditional microbiological assay. Factors affecting pimaricin production were investigated in shake flasks. Dosing the fermentation with sodium citrate was shown to have a significant effect on production. A rapid method for screening large numbers of survivors from a mutagenesis programme was developed. EMS and UV mutagenesis provided a number of isolates with increased productivity. Scale-up of the process in a 16 litre stirred fermenter proved difficult with the culture showing a strong requirement for oxygen. However, yields were equivalent to, and in some cases higher than those obtained in shake flasks. Although, improvements were made to the overall process, yields that would make the process economically viable were not obtained. This project was funded by Biocon Biochemicals Ltd., Cork, Ireland. All of the research work was conducted at Dublin City University, formerly the National Institute for Higher Education (NIHE), Dublin