珍贵橙色束丝放线菌生产安丝菌素P-3的发酵工艺

Fermentation Process of Ansamitocin P-3 by Actinosynnema pretiosum

将安丝菌素P-3(1)产生菌珍贵橙色束丝放线菌(Actinosynnema pretiosum)的紫外诱变高产菌株A.pretiosum SIPI-U-7 6,通过5 L发酵罐进行小试工艺研究,表明搅拌剪切力对1产量有明显的影响。采用降低搅拌转速、减少种子培养时间和调整发酵配方的方法,在5 L发酵罐上1的发酵单位可优化达到378 mg/L。将优化后的小试工艺放大至500 L和1 000 L罐上,发酵单位分别达到288和317 mg/L,较未优化的5 L发酵罐上的1发酵单位(23 mg/L)提高了11.5倍和12.8倍,实现了1的规模化生产。

Ansamitocins isolated from Actinosynnema pretiosum are a group of potent antitumor maytansinoids that block the assembly of tubulin into functional microtubules. Ansamitocins include five components and AP-3 （1） is the main fermentation product. The clinical applications of 1 have stimulated extensive studies to improve its production. Although efforts have been made for the study of ansamitocins biosynthetic gene clusters and their fermentation improvement, the yield of 1 is still limited. In this study, a small-scale fermentation process was carried out in a 5 L fermentor by using a UV mutagenesis strain, Actinosynnema pretiosum SIPI-U-76. The results showed that the shear force had a significant effect on the yield of 1. By controlling the stirring speed not higher than 400 r/min, reducing the seed culture time to 40 h, and reducing the corn starch in fermentation medium to 20 g/L, the yield of I reached 378 mg/L in a 5 L fermentor. The above process was applied to pilot-scale production in a 500 L fermentor and a 1 000 L fermentor, the yield of 1 reached 288 and 317 mg/L.