摘要
为优化达托霉素发酵条件,通过单因素实验和响应面方法研究了达托霉素发酵条件温度、pH值、接种量、通风量和搅拌转速.结果表明:优化后的发酵工艺条件为温度27.74℃、pH值8.36、接种量8.48%、通风量6.13 L/min、搅拌转速242 r/min,在此条件下达托霉素的产量可达880.48 mg/L,比最新报道的达托霉素发酵效价提高了132%.本方法大幅度提高了达托霉素产量,对达托霉素工业化生产提供了可靠的研究基础.
In order to optimize the fermentation conditions of doxymycin, the fermentation conditions of doxymycin, temperature, pH, inoculation, ventilation and stirring speed, were studied by single factor test and response surface method. The results showed that the optimized fermentation process conditions were 27.74 ℃, pH 8.36, inoculation 8.48%, ventilation 6.13 L/min, and stirring speed 242 r/min. Under this condition, the yield of doxymycin can reach 880.48 mg/L, which was 132% higher than the newly reported fermentative effective potency of doxymycin. This study has greatly increased the production efficiency of doxymycin and provided a reliable research basis for the industrial production of doxymycin.
引文
[1] 何美儒,金志华,胡升,等.补加葡萄糖对玫瑰孢链霉菌发酵产述托霉素的影响[J].中国医药工业杂志,2012,43(8):662-665.
[2] 周剑,黄建峰,张引,等.低能离子注入诱变达托霉素高产菌株及其发酵的研究[J].中国抗生素杂志,2012,37(8):587-592.
[3] PARTHIBAN K,VIGNESH V, THIRUMURUGAN R.Characterization and in vitro studies on anticancer activity of exopolymer of Bacillus thuringiensis S13[J].African Journal of Biotechnology,2014,13(21):37-44.
[4] 于红,杨文菊,刘波,等.RRLC定性检测食用油中10种抗氧化剂的条件研究与应用[J].新疆医科大学学报,2011,34(2)172 -174.
[5] 余继叁,洪葵,林海鹏,等.玫瑰孢链霉菌NRRL11379产达托霉素前体物A21978C的发酵培养基优化[J].安徽农业科学,2008,36(19):7974-7976.
[6] 周剑,张引. 达托霉素产生菌前体物耐受选育及其流加补料发酵[J].中国抗生素杂志,2018,7(43):817-823.
[8] 郭朝江,张兰,王成,等.缓释癸酸前体对玫瑰孢链霉菌发酵产达托霉素的影响[J].中国医药工业杂志,2013,44(3):238-241.
[7] ZHANG X,ZHANG X F,Li H P,et al.Atmospheric room temperature plasma(ARTP) as a new powerful mutagenesis tool[J].Appl Microbiol Biotechnol,2014,98(12):5387—5396.
[9] LU C Y,ZHANG X J,JIANG M,et al.Enhanced sali-nomycin production by adjusting the supply of polyketide extender units in Streptomyces albus[J].Metab Eng,2016,8(35):129-137.
[10] 谷宇锋,王淑歌,郝海红,等. 亚抑菌浓度抗生素对细菌耐药性和毒力影响的研究进展[J].中国抗生素杂志, 2018,43(11): 1321-1331.
[11] REN J,CUI Y Q,ZHANG F,et al.Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces hygroscopicus[J].Microbiol Res,2014,169(7-8):602-608.
[12] YIN C,ZHANG T,QU X,et al.In vivo excision of HIV1 provirus by saCas9 and multiplex single-guide RNAs in animal models[J].Mol Ther,2017,25(5):1168-1186.
[13] 王世博,李平兰,张金兰,等. 二肽基肽酶-IV抑制活性酵母筛选与鉴别[J]. 中国酿造, 2018, 37(9): 48-51.
[14] JIAO Z,WANG X,YIN Y,et al.Preparation and evalua-tion of a chitosan-coated antioxidant liposome containing vitamin C and folic acid[J].J Microencapsul,2018,6(9):1-9.
[15] SUN H, YAN P, LU P,et al.Effects of exogenous addition of vitamin C on ε-poly-L-lysine fermentation by Streptomyces[J].Food and Fermentation Industries, 2018, 44(9): 29-35.
[16] 薛海萍,高婷婷,杨骏,等.红景天苷磷脂复合物的体外透皮试验[J].中国实验方剂学杂志,2016,22(9):9-11.
[17] DAS M K,KALITA B,et al.Design and evaluation of phytophospholipid complexes (phytosomes)of rutin for transdermal application[J].J Appl Pharm Sci,2014,4(10):51-57.