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康乐霉素 C(简称 K- C)是一个新的免疫抑制剂 ,但它在发酵液中的含量很低 ,仅为 0 .1mg/ L。为了满足药效学、毒理学试验和药代动力学所需的样品 ,就必须提高 K- C的产量。 K- C的产生菌为 N ocardiamediterranei var.K anglensis 1747- 6 4,用本所的自然突变株 ST- 91为出发菌株 (下称出发菌株 ) ,采用紫外线诱变和自然分离纯化的方法 ,筛选出 1株 K- C的产量明显地高于出发菌株的突变株 U1 0 - S- 4。对 U1 0 - S- 4的生产稳定性进行了考察 ,其稳定性很好 ,可传到第四代。并对它的发酵条件 ,如 :p H值、接种量、发酵周期等进行了研究 ,进而进行了 5 0 0 L罐上放大试验 ,绘制出突变菌株 U1 0 - S- 4的生长代谢曲线 ,通过对代谢曲线分析 ,优化了发酵条件 ,进行了罐上的补料试验 ,确立了 5吨罐上的操作条件 ,成功地进行了 3批生产 ,K- C效价可以达到 46 .0 mg/ L ,比出发菌株提高了 46 0多倍。
Quinimycin C (K-C) is a new immunosuppressive agent, but it is very low in the fermentation broth, only 0.1 mg / L. In order to meet the needs of pharmacodynamics, toxicology tests and pharmacokinetics of the sample, it is necessary to increase K-C production. The producing strain of K-C is Nocardia mediterranei var. K anglensis 1747-64. Using the natural mutant strain ST-91 of this institute as a starting strain (hereinafter referred to as the starting strain), the strain of Koccopteris var.K anglensis 1747-6 was screened by UV mutagenesis and natural separation and purification The yield of a strain of K-C was significantly higher than that of the mutant U1 0 - S-4 of the starting strain. The stability of production of U1 0 - S - 4 was investigated, its stability is very good and it can be transmitted to the fourth generation. The fermentation conditions such as p H value, inoculum size, fermentation period and so on were studied. Then the amplification experiment was carried out on a 500 L jar, and the growth metabolic curve of the mutant strain U1 0 - S-4 was drawn. Through the analysis of the metabolic curve, the fermentation conditions were optimized, the feeding experiment on the tank was carried out, the operating conditions on the 5-ton tank were established, and the batch production was successful. The K-C titer reached 46.0 mg / L, 460 times higher than the original strain.