新来源棘白霉素B脱酰基酶产生菌的筛选和转化条件优化  

Screening of novel echinocandin B deacylase-producing strain and optimization of biotransformation conditions

作　　者：丁彦博[1] 可爱兵[1] 蔡超靖[1] 穆云龙[1] 单越琦[1] 李业英[1] 石英[1] 崔晓兰[1] 徐岩[1] 朱京童[1] 路新华[1] 

机构地区：[1]华北制药集团新药研究开发有限责任公司,微生物药物国家工程研究中心,河北省工业微生物代谢工程技术研究中心,石家庄050015

出　　处：《中国抗生素杂志》2012年第6期449-454,共6页Chinese Journal of Antibiotics

基　　金：国家科技部重大新药创制专项(2010ZX09401-403;2010ZX09401-306)

摘　　要：目的筛选放线菌来源的棘白霉素B脱酰基酶产生菌,并对其转化条件进行优化。方法根据菌株转化产物对白念珠菌的抑制活性进行初筛,再以HPLC、LC-MS检测确定目的菌株;对目的菌株转化棘白霉素B的培养基、转化温度和时间、缓冲液、甲醇含量等条件进行优化以提高转化率。结果筛选得到4株可产生脱酰基酶的阳性菌株,其中,N07W-.61为小单孢菌属菌株,其余3株为链霉菌属菌株;通过转化条件优化,菌株N07W-61对棘白霉素B的转化率从2.60%提高至61.24%。结论小单孢菌属菌株产生棘白霉素B脱酰基酶为首次报道;该属菌株N07W-61在优化转化条件下对棘白霉素B的转化率有了大幅提高。Objective Screening of echinocandin B deacylase-producing strains from actinomycetes and optimization of biotransformation conditions. Methods When echinocandin B was deacetylized by the deacylase, it would not inhibit the growth of Candida albicans. Preliminary positive strains were picked out by measurement of the inhibitory activity to the Candida albicans. And then subsequent determination by HPLC and LC-MS were carried out for the target strains. Biotransformation conditions including media, biotransformation temperature and time, buffer solution and content of methanol were optimized to increase the transformation ratio of Echinocandin B. Results Four echinocandin B-deacylase-producing strains, including a Micromonospora sp. strain N07W-61 and three Streptomyces sp. strains were obtained. The biotransformation ratio of echinocandin B by the strain N07W- 61 was increased from 2.60% to 61.24% in the optimized media at 37℃ for 16 hours. Conclusion Echinocandin B deacylase from Micromonospora sp. strain N07W-61was first reported. And the biotransformation ratio of echinocandin B was increased substantially.

关 键 词：小单孢菌属 棘白霉素B 脱酰基酶 转化 优化 

分 类 号：R379.1[医药卫生—病原生物学]