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

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.