产纽莫康定B_(0)丝状真菌Filamentous fungus的菌种选育和发酵工艺优化  

Strain Breeding and Fermentation Process Optimization for Production of Pneumocandin B_(0) by Filamentous fungus

作　　者：谢秋萍 卫腾云 谢亚茹 张海霞[2] 陈少欣[2] XIE Qiuping;WEI Tengyun;XIE Yaru;ZHANG Haixia;CHEN Shaoxin(School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620;State Key Lab.of New Drug and Pharmaceutical Process,Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]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

出　　处：《中国医药工业杂志》2021年第5期652-660,共9页Chinese Journal of Pharmaceuticals

摘　　要：纽莫康定B0(pneumocandin B0,PB0)是由丝状真菌Filamentous fungus产生的次级代谢产物,可用于合成抗真菌药物卡泊芬净。为提高PB0的产量,对丝状真菌SIPI 2776菌株进行亚硝基胍(NTG)、60Co伽马射线(60Co-γ)、紫外(UV)和常压室温等离子体(ARTP)等诱变,获得突变菌株11-γ-12,PB0摇瓶产量为1.48 g/L。此外,利用基因工程改造技术得到纽莫康定C0(PC0)含量降低的工程菌株F-ap-htyE。使用响应面法优化发酵培养基,使PB0摇瓶产量达到2.01 g/L,并研究了发酵罐的分批补料培养,通过优化甘露醇的补加量,使PB0发酵产量达到2.71 g/L。Pneumocandin B0(PB0) is a secondary metabolite produced by Filamentous fungus,which can be used to synthesize the antifungal drug,caspofungin.In order to increase the yield of PB0,the Filamentous fungus SIPI 2776 strain was subjected to nitrosoguanidine(NTG),60Co gamma-ray(60Co-γ),ultraviolet(UV) and atmospheric rooom temperature plasma(ARTP) mutagenesis.The mutant strain 11-γ-12 was obtained,and the yield of PB0 shake flask was 1.48 g/L.In addition,genetic engineering technology was used to obtain an engineered strain F-ap-htyE with reduced pneumocandin C0(PC0) composition.The response surface method was used to optimize the fermentation medium,and the yield of PB0 shake flask reached 2.01 g/L.The fed-batch culture in a 5 L fermenter was studied,and the fermentation yield of PB0 reached 2.71 g/L by optimizing the supplemental amount of mannitol.

关 键 词：纽莫康定B_(0) 卡泊芬净 丝状真菌 菌种选育 培养基优化 发酵 

分 类 号：R915[医药卫生—微生物与生化药学] TQ927[医药卫生—药学]