19-08-2014, 11:34 AM
Tylosin, a 16-membered macrolide antibiotic, was first isolated in the laboratories of Eli Lilly and Company, Indianapolis, Indiana. It is commercially produced by Streptomyces fradiae NRRL 2702 and has also been reported to be produced by strains of Streptomyces rimosus and Streptomyces hygroscopicus.
Tylosin, a 16-membered macrolide antibiotic, was first isolated in the laboratories of Eli Lilly and Company, Indianapolis, Indiana. It is commercially produced by Streptomyces fradiae NRRL 2702 and has also been reported to be produced by strains of Streptomyces rimosus and Streptomyces hygroscopicus.
Tylosin finds exclusive applications in animal nutrition and veterinary medicine. It is used in the control of respiratory disease in poultry, improves weight gains in poultry and swine, and controls a number of other diseases in cattle, swine, poultry and dogs. Tylosin acts on microorganisms by inhibiting protein synthesis. It has been found to bind to the 50-S subunit of the ribosome and thus inhibits binding of the aminoacyl end of aminoacyl t-RNA and inhibit the formation of the mRNA-aminoacyl-tRNA-ribosome complex.
The present work was undertaken with following objectives I) Screening of strains from Streptomyces sp. for production of tylosin and other secondary metabolites. II) Optimization of fermentative production by one factor-at-a-time and kinetic studies on the production of secondary metabolites. III) Purification tylosin by solvent extraction and ion exchange chromatography.
Five strains of Streptomyces sp. were screened for production of tylosin in submerged and solid state fermentation. As none of the strains gave detectable production of tylosin by either fermentation method, other metabolites from Streptomyces sp. were investigated. Streptomyces clavuligerus MTCC 1142, which produced clavulanic acid (a -lactamase inhibitor), was then used for further studies involving media optimization and kinetic modeling of batch fermentation process. In first step, optimization of clavulanic acid production was carried out for various parameters like carbon source, nitrogen source, their concentrations and addition of amino acids precursors. The optimization was carried out by one factor at-a-time followed by a study on effect of different glycerol feeding strategies on clavulanic acid production. One factor at-a-time method resulted in an increase of clavulanic acid production from 78.10 ± 0.62 g/ml to 123.32 ± 1.88 g/ml. Further increase in clavulanic acid production up to a level of 175.87 ± 2.4 g/ml was achieved using fed batch fermentation. A kinetic study on batch fermentation using the optimized medium was then carried out in a 5 L fermenter. Studies for purification of tylosin using solvent extraction using chloroform as a solvent and ion exchange chromatography using weak cation exchange resin, Indion 652, were also carried out.