Streptomyces sp.FIM-16-06产他克莫司摇瓶发酵条件的优化
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摘要
采用单因素试验和正交试验研究发酵培养基组成,优化Streptomyces sp. FIM-16-06产他克莫司的发酵条件,探讨摇瓶发酵的主要影响因子初始p H、装液量、转速等发酵参数的影响。确定了适宜的发酵培养基和发酵参数:6. 0%玉米淀粉、2. 0%黄豆粉、2. 0%葡萄糖和0. 5%玉米浆,初始pH 7. 5,装液量50 m L/500 m L三角瓶,种子菌龄48 h,接种量10%,摇床转速250 r/min,发酵温度27℃,发酵周期7 d。优化后的发酵水平较原生产工艺提高60%以上。他克莫司的优化发酵工艺为其工业化生产奠定了基础。
In order to optimize the fermentation conditions for tacrolimus-producing strain Streptomyces sp. FIM-16-06,the single factor experiments and orthogonal experiments were adopted to investigate the liquid fermentation medium and culturing parameters of Streptomyces sp. FIM-16-06. The results revealed that the appropriate fermentation medium composition and optimal fermentation parameters were determined as follows: fermentation medium containing corn starch6. 0%,glucose 2. 0%,soybean flour 2. 0% and corn steep liquor 0. 5%,while the initial pH 7. 5,filling volume 50 m L/500 m L shake flask,cultivation time of seed 48 h,inoculum size 10%,shaker's rotating speed 250 r/min,fermentation temperature 27 ℃ and fermentation time 7 d. The tacrolimus yield of Streptomyces sp. FIM-16-06 under the optimized fermentation conditions was 60% higher than that of the original. The optimal fermentation conditions of Streptomyces sp.FIM-16-06 laid the foundation for further industrial fermentation.
In order to optimize the fermentation conditions for tacrolimus-producing strain Streptomyces sp. FIM-16-06,the single factor experiments and orthogonal experiments were adopted to investigate the liquid fermentation medium and culturing parameters of Streptomyces sp. FIM-16-06. The results revealed that the appropriate fermentation medium composition and optimal fermentation parameters were determined as follows: fermentation medium containing corn starch6. 0%,glucose 2. 0%,soybean flour 2. 0% and corn steep liquor 0. 5%,while the initial pH 7. 5,filling volume 50 m L/500 m L shake flask,cultivation time of seed 48 h,inoculum size 10%,shaker's rotating speed 250 r/min,fermentation temperature 27 ℃ and fermentation time 7 d. The tacrolimus yield of Streptomyces sp. FIM-16-06 under the optimized fermentation conditions was 60% higher than that of the original. The optimal fermentation conditions of Streptomyces sp.FIM-16-06 laid the foundation for further industrial fermentation.
引文
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[11]王德森,张祝兰,唐文力,等.替考拉宁产生菌A. teichomycoticus FIM-37发酵条件优化[J].药物生物技术,2017,24(4):310-314.
[12]王怡梅,周鑫鑫,邓刚.响应面法对微拟球藻产微藻蛋白的发酵条件优化[J].工业微生物,2017,47(3):36-42.
[13]王增元,孙建安,毛相朝,等.混合菌固体发酵花生粕的工艺优化[J].工业微生物,2017,47(6):19-24.
[2]刘菲,魏继福,孟玲,等.大环内酯类免疫抑制剂的研究进展[J].药学与临床与研究,2014,22(1):61-66.
[3]黄勇,姜尔烈,王玫,等.他克莫司和环孢素A防治急性移植物抗宿主病的效果比较[J].中华器官移植杂志,2007,28(5):286-289.
[4]高森,高毅,刘永光,等.他克莫司替代环孢素A为基础方案治疗不同病理类型慢性移植肾肾病:有效性和安全性[J].中国组织工程研究,2010,4(18):3408-3411.
[5]侯健.环孢菌素A和FK506免疫抑制的分子机制[J].国际药学研究杂志,1993,20(4):193-195.
[6]苏俊波,骆文龙.免疫抑制剂FK506在器官移植中应用的新进展[J].重庆医学,2002,31(12):1259-1261.
[7]杨敏,虞青,黄世恒,等.系统性红斑狼疮相关新型药物及治疗方式的研究进展[J].医学研究杂志,2016,45(8):168-172.
[8]尹婉嫱,郭顺星.正交设计法优化培养基中美拉德反应条件以提高猪苓菌核产量的研究[J].中国药学杂志,2011,46(17):1309-1311.
[9]罗玮,周雅,巩尊洋,等.丝状真菌三孢布拉霉产番茄红素发酵条件优化[J].食品与发酵工业,2015,41(12):126-130.
[10]高春慧,金伟,高春景,等.用Minitab软件进行链霉素发酵培养基的配方设计与优化[J].药物生物技术,2016,23(5):397-402.
[11]王德森,张祝兰,唐文力,等.替考拉宁产生菌A. teichomycoticus FIM-37发酵条件优化[J].药物生物技术,2017,24(4):310-314.
[12]王怡梅,周鑫鑫,邓刚.响应面法对微拟球藻产微藻蛋白的发酵条件优化[J].工业微生物,2017,47(3):36-42.
[13]王增元,孙建安,毛相朝,等.混合菌固体发酵花生粕的工艺优化[J].工业微生物,2017,47(6):19-24.