不同培养基组成对去甲基博来霉素发酵产率的影响.pdfVIP

不同培养基组成对去甲基博来霉素发酵产率的影响 1 1 12 2 1 张宁宁 , 杨冬 , 朱湘成 , 段燕文 ，徐志南 （1浙江大学化学工程与生物工程学系，浙江 杭州 310027； 2长沙天赐生物医药科技有限公司，长沙 湖南 410329） 摘要：去甲基博莱霉素是一种新型的抗肿瘤抗生素，具有重大的潜在临床应用价值。我们通过系统研究培 养基中碳源、氮源、无机盐等组分对发酵产率的影响，形成了一个优化的培养基。在这一培养基上，去博 莱霉素的发酵水平提高了8 倍，达到45 mg·L-1 。最后，我们通过色谱层析等方法进行产品的初步分离。 关键词：去甲基博莱霉素；发酵条件优化；分离纯化 Effects of different medium components on the productivity of Desmethyl BLM H-A ZHANG Ningning, YANG Dong, ZHU Xiangcheng, DUAN Yanwen, XU Zhinan (1Department of Chemical and Biochemical Engineering,Zhejiang University,Hangzhou Zhejiang 310027,China; 2 Changsha Charism Bioscience Corporation Ltd, Changsha, Hunan 410329, China) Abstract: Desmethyl-BLM H-A is one of the novel hybrid peptide-polyketide antibiotics with potential applications for the treatment of many malignant tumors. The effects of different medium components (carbon sources, nitrogen sources, phosphate salts, CuSO and ZnSO ) on the 4 4 production of Desmethyl-BLM H-A were investigated systematically. One optimal fermentation medium was formulated which can support high productivity of Desmethyl-BLM H-A (45 mg·L-1) after 6-day culture, about 8-fold higher than that obtained in the original medium. The preliminary separation of the Desmethyl-BLM H-A was also achieved by using two-step chromatographic processes. Key words: Desmethyl BLM H-A; fermentation conditions; separation 引言 近25 年来采用组合生物合成技术发现新的抗生素已得到快速发展，显示了强大的威力. 如克隆和分析链霉菌中与抗生素相关的基因簇，然后在大肠杆菌中构建表达载体，并转移到 链霉菌中实现稳定和高效的异源合成等。 Tallysomycins (TLMs) 是Streptoalloteichus hindustanus E465-94 产生的一类糖肽类抗癌 联系人：徐志南。第一作者：张宁宁 Corresponding author: Pr