Optimization And Analysis Of The Strains And The Fermentation Process Of The Flavomycin

Flavomycin, as a new type digestive enhancer, is a kind of ketose and aldose phosphates antibiotics, is industrially produced by Streptomyces bambergiensis strain. The development of the antibiotic has good economic and social performance for its effective safety, low toxicity and low rudimentality, rather simple fermentation techniques for production, low cost by using massively available agricultural byproducts as the major substrate, and environment-friendliness with low contamination.This thesis focuses on the strain improvement and optimization of the fermentation conditions for higher and stable yield of Flavomycin. Firstly, the high-yield strains were screening by UV and LiCl, As a result, we obtained a high-yield strain with there productivity increased by 50% percent. While we have optimized the process of the strain, the culture cycle of slant and seed time effect on fermentation was studied by single factor experiments. The result indicted that: the spore time is 72 hours, the seed time is 37 hours, which is suitable to the fermentation of flavomycin.Secondly, According to the metabolic regulation of flavomycin, we analyzed the fermentation process. We have screened the raw materials of the carbon sources and the nitrogen sources. For the carbon sources, we mainly experimented with corn flour, glucose, soybean oil, soluble starch and so on, the result is that we chose corn flour as the main carbon source and soybean oil as the supplement carbon source.For the nitrogen sources, there are many choices. From the results of our experiments, we chose a mixture of the inorganic (NH₄)₂SO₄ and organic bean cake powder plus Biological N as the nitrogen sources. The concentration of total nitrogen used is more than 3.0%.After we optimized the nitrogen and carbon source, we investigated the uses of the trace elements and inorganic salt for the fermentation medium. During the experiments, we found that K₂HPO₄ and MgSO₄ are the key factors those are able to significantly affect the production of flavomycin. The optimal medium of the fermentation is 0.02%K₂HPO₄, 0.05%MgSO₄, 4.0%corn flour, 2.0% bean cake powder, 1.0%Biological N, 0.3%(NH₄)₂SO₄, 0.0002%ZnSO₄, 4.0% bean oil , 0.5%CaCO₃, 0.01% subdues bubble pharmaceutical., 0.0000 1%CoSO₄, 0.7% surfactant, 0.0005% CuSO₄·5H₂O,0.9%corn liquid, 0.00004% FeSO₄·7H₂O.Thereafter, the techniques for controlling the feeding of the oil and other substrate were optimized. Our experiments showed that the yield of flavomycin could be increased small by feeding batch fermentation. The ability of produce flavomycin could be lengthened. Thus, the feeding technique is employed in our further work. In the beginning, water and the other substrates were fed only based on fermentation culture time, After series of experiments, we controlled the feeding of water and the other substrate by assaying the metabolic curve of the flavomycin, Besides, the growth stage of the mycelium and the high level of nitrogen in NH₂ were also referred for the feeding time and the feeding amount. From the result, we suggested a formula for programmed feeding. For in detail controlling the fermentation process, the controlling program was set in several stages, based on the metabolic stages of the cell and metabolic rate.We investigated how to improve the amount Flavomycin A from the flask level and 10L bioreactor. The results show that the middle-batch has a certain negative and feeding water during the fermentation has little effect on the improvement of the proportion of Flavomycin A.