| Lipstatin is an inhibitor of pancreatic lipases isolated from Streptomyces toxytricini. Based on the biosynthetic pathway and metabolic regulation,a rational selection procedure was performed to obtain a new lipstatin high-producing strain Streptomyces toxytricini XC-LP-2 is the parent strain. A rational screening was adopted to select a strain which could grow well on the medium with high concentration of soybean oil, Sodium n-caprylicacid, Leucine. By above methods, a high-producing strain XC-LP-7-69 was obtained. The productivity reaches 831μg/mL, which is increased by 168% in comparision with that of the parent stiain XC-LP-2, subculture test indicted that the hereditary character of high productivity of Streptomyces toxytricini XC-LP-7-69 was stable.Streptomyces toxytricini XC-LP-7-69's optional medium was established by orthonormal experiment. The productivity of XC-LP-7-69In shake flaske was raised 21.5%. The effects of inorganic salts, temperature, seed age, dissolved oxygen, inoculation sige, shearing strength and feeding was studiell in shake flaske. The optimal concentration of lipastation fermentation, the optimal temperature for lipstatin biosynthesis is 27℃. With the optimal fermentation medium and condition, the titer of lipstatin was increased greatly by feeding. As a result, the productivity of Streptomyces toxytricini XC-LP-7-69 reaches 1400μg/mL .Based on the results in shake flasks. Lipstatin fermentation was scaled up in a 15L fementor. And a productivity of 1561 ug/mL was obtained.
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