多黏菌素B生产菌多黏芽孢杆菌的选育和发酵过程优化  

Strain Breeding and Fermentation Process Optimization for Production of Polymyxin B by Paenibacillus polymyxa

作　　者：李聪慧 李振鑫 张正玉 杨松柏[1] 奕栋[1] 陈少欣[1] LI Conghui;LI Zhenxin;HANG Zhengyu;YANG Songbai;YI Dong;CHEN Shaoxin(State Key Lab.of New Drug and Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203;School of Pharmacy,Fudan University,Shanghai 201203)

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201203 [2]复旦大学药学院,上海201203

出　　处：《中国医药工业杂志》2023年第8期1208-1215,共8页Chinese Journal of Pharmaceuticals

基　　金：科技部重点研发计划“绿色生物制造”项目(2021YFC2102100);“上海市浦江人才计划”项目(21PJ1423200)。

摘　　要：多黏菌素B(1)是由多黏芽孢杆菌(Paenibacillus polymyxa)产生的一类碱性多肽类抗菌药,主要成分包括B1、B2、B3和B1-I,对耐药菌感染的治疗效果显著。为了提高1产量,该研究以多黏芽孢杆菌SIPIPB-1[发酵单位(837±50)mg/L]为出发菌株,采用传统诱变法选育,获得了突变菌株SIPIPB-N14[发酵单位(1297±60)mg/L]。随后优化了SIPIPB-N14的发酵培养基和发酵工艺。在优化发酵条件下,1在5L发酵罐中的发酵产量可达(1681±25)mg/L,其中B1、B2、B3、B1-I的比例分别为(74.5±1.1)%、(20.4±0.8)%、(1.3±0.3)%、(3.0±0.1)%,符合原料药组分的要求,为工业化生产提供了试验数据。Polymyxin B(1),a basic polypeptide antibacterial drug,was mainly produced by Paenibacillus polymyxa and showed significant effects on treatment of drug-resistant bacterial infections.The main components of 1 include B1,B2,B3,and B1-I.To increase the yield of 1,this study with P.polymyxa SIPI PB-1[fermentation unit:(837±50)mg/L]as the starting strain,obtained the mutant strain SIPI PB-N14[fermentation unit:(1297±60)mg/L]through traditional mutagenesis and selection.Then,the fermentation medium and fermentation process of SIPI PB-N14were optimized.Under the optimized fermentation conditions,the fermentation yield of 1 in a 5 L fermenter could reach(1681±25)mg/L,of which the proportions of B1,B2,B3,and B1-I were(74.5±1.1)%,(20.4±0.8)%,(1.3±0.3)%,and(3.0±0.1)%,which met the requirements of API components and provided test data for industrial production.

关 键 词：多黏芽孢杆菌 多黏菌素B 诱变育种 培养基优化 发酵 

分 类 号：Q815[生物学—生物工程]