High-yielding Strain Breeding And Culture Condition Optimization For Tylosin

Tylosin is a commercially-important, 16-membered macrolide antibiotic produced by Streptomyces fradiae. It exclusively applied in animals to control the mycoplasma induced diseases, improve feed conversion efficiency, and increase average daily weight gain.A stable mutated strain A-49 was obtained from the spores of tylosin producer Streptomyces fradiae BMB-012 by purification. The strain A-49 was chosen as the start strain for mutagenic treatments with ultraviolet irradiation + LiCl, DES and Streptomycin resistant rational screening, after first and second selection, the mutant S-22 was selected. It showed better growth and yield characters than the strain A-49.The tylosin yield of the strain S-22 was 9168μg/ml which improved 68%.The fermentation medium optimized experiment with the strain S-22 was on shaking flask level. The effects of carbon sources, nitrogen sources, inorganic salts, were studied by means of single factor. The medium SH1 was established by orthonormal experiment. The production of tylosin in medium SH1 was 10886μg/ml.Back-Propagation (BP) neural network and genetic algorithms (GA) were employed to optimize the medium for production of tylosin. BP neural network was applied for modeling fermentation medium of tylosin. Based on the model, the fermentation medium compositions which included rape oil, fish meal D, betaine hydrochloride and ingredient X ,were optimized by GA. The optimized result was: rape oil 36g/L, fish meal D 18.5g/L, betaine hydrochloride 1.8g/L, ingredient X8.8g/L. The production of tylosin in optimized medium was 12878μg/ml, which was increased by 18.3% compared to that in medium SH1.The relative error between the experimental value and the predictive value of tylosin production from the optimized medium was2.08%.Those results showed it was effective by the method of BP neural network and genetic algorithms in optimizing the medium for production of tylosin.The optimal fermentation conditions of the strain S-22 were studied by means of single factor. From the shake-flask, the optimal fermentation conditions were: initial pH 7.2,12% inoculums, 28℃, 40ml/500ml shake flask, culture 7 days. With the optimal fermentation medium and condition, the productivity of tylosin could be up to 13216μg/ml.