邻氨基苯甲酸对达托霉素发酵的影响  

Effect of Anthranilic Acid on Fermentation of Daptomycin

作　　者：徐鲁 卢雪欢 张建斌[1] 李继安[1] 林惠敏[1] XU Lu;LU Xuehuan;ZHANG Jianbin;LI Ji'an;LIN Huimin(State Key Lab.of New Drug and Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 200040;Collaborative Innovation Center of Yangtza River Delta Region Green Pharmaceuticals,Zhejiang University of Technology,Hangzhou 310014)

机构地区：[1]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海200040 [2]浙江工业大学长三角绿色制药协同创新中心,浙江杭州310014

出　　处：《中国医药工业杂志》2019年第12期1434-1438,共5页Chinese Journal of Pharmaceuticals

基　　金：国家“重大新药创制”科技重大专项(2012ZX09201101-008);国家自然科学基金(81273413);上海市自然科学基金(14ZR1440200)

摘　　要：本实验室在达托霉素发酵研究中,观察到发酵液中某未知物浓度与达托霉素浓度在整个过程中存在此消彼长的关系。经液质联用检测分析,确定未知物为合成色氨酸的前体物--邻氨基苯甲酸。在摇瓶发酵24 h时添加邻氨基苯甲酸钠,对达托霉素的产生有最大的促进作用;在进一步的25 L发酵罐试验中,以不同流速流加邻氨基苯甲酸钠,结果在以0.08 g·L-1·h-1的速度添加邻氨基苯甲酸钠的试验组中,达托霉素的产量在发酵192 h达到3432 mg/L,与对照组相比,产量提高了23%。An unknown compound in fermentation liquor was found during daptomycin fermentation. On the basis of detection of the fermentation broth by LC-MS, we found that there was a antagonistic relationship between the synthesis of daptomycin and the unknown compound, which was confirmed as anthranilic acid, the precursor of tryptophan. In flask test, adding sodium anthranilate at 24 h of fermentation could promote the production of daptomycin greatly. In a 25 L fermentor, the production of daptomycin was up to 3 432 mg/L when the batch-feeding rate of sodium anthranilate was 0.08 g·L-1·h-1, which increased by 23% separately compared with the control. It provided a beneficial reference for industrialized production of daptomycin.

关 键 词：达托霉素 邻氨基苯甲酸 补料 前体物 

分 类 号：R978.1[医药卫生—药品]