纳他霉素产生菌的诱变育种及其发酵条件的优化  

Mutation breeding and optimization of fermentation for high production of natamycin by Streptomyces natalensis

作　　者：阎永贞[1] 魏晓东[1] 那可[1] 金媛媛[1] 赵波[1] 赵文杰[1] 

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

出　　处：《中国抗生素杂志》2013年第5期332-338,共7页Chinese Journal of Antibiotics

基　　金：国家"重大新药创制"科技重大专项"微生物药物技术创新与新药创制产学研联盟"(No.2010ZX09401-403)

摘　　要：目的以纳塔尔链霉菌(Streptomyces natalensis)SIPI-NHF-09为出发菌株进行诱变选育和培养条件优化,以提高其纳他霉素的产量。方法采用紫外和微波结合对纳塔尔链霉菌SIPI-NHF-09进行诱变选育,并对获得的高产突变株SIPI-UW-10-22的发酵条件进行了初步优化。结果经过连续3轮的紫外和微波诱变,获得高产突变株SIPI-UW-10-22,其纳他霉素(Natamycin)产量达到3.15g/L,是出发菌株的3.5倍,且该菌株经多次传代,遗传性能稳定。对SIPI-UW-10-22发酵条件优化后获得其发酵条件为:以5.5%玉米淀粉加0.5%葡萄糖为碳源,2%黄豆饼粉加1%酵母粉为氮源,种龄46h,初始pH7.0,接种量8%,摇床转速220r/min,28℃培养126h。此条件下,纳他霉素的产量达到4.07g/L,较优化前提高了1.29倍。结论紫外与微波诱变相结合的方法简便有效,所获得高产菌株遗传性状稳定。Objective The mutation breeding and cultural conditions optimization were used to obtain a higher natamycin-producing strain. Methods A high-yield Streptomyces natalensis mutant strain SIPI-UW-10-22 was obtained after breeding SIPI-NHF-09 by ultraviolet and microwave mutation, and it was genetic stable for 5 generations. The fermentation conditions of SIPI-UW-10-22 was also optimized. Results After three rounds continuous selection, the yield of mutant strain SIPI-UW-10-22 reached 3.15g/L, which was 3.5 times higher than the parent strain SIPI-NHF-09. The optimal fermentation conditions were as follows： 5.5% corn starch plus 0.5% glucose as compounded carbon sources, 2% soybean cake powder plus 1% yeast powder as compounded nitrogen sources, seed age 46h, initial pH7.0, inoculum quantity 8%, rotating speed 220r/min, culture temperature 28~C, fermentation time 126h. Under this condition, 4.07g/L natamycin was obtained, which was 1.29 times higher than that under the initial conditions. Conclusion Ultraviolet combined with microwave mutation can be an effective breeding method, by which the high-yield mutant strain obtained was genetic stable.

关 键 词：纳塔尔链霉菌 纳他霉素 诱变育种 发酵条件优化 

分 类 号：R978.5[医药卫生—药品]