新型抗真菌抗生素发酵工艺及动力学研究

从浙江省东海土壤中筛选到1株具有抑制白色念珠菌ATCC 64548生长的解淀粉芽孢杆菌091,发现其能产生一种相对分子质量为410的大环内酯类抗真菌物质。在250 mL摇瓶中进行了抗生素发酵的单因素优化实验,实验结果:28℃,pH值6.5,摇床转速200 r/min,接种量(体积分数)8%,装液量40 mL,发酵时间36 h。优化后发酵液抗真菌效价比初始培养条件下提高了2.49倍,达7 026.79 U/mL。进一步采用Logistic,Luedeking-Piret和Lu-edeking-Piret-like方程建立了抗生素产生的动力学模型,并根据5 L发酵罐中的实验数据拟合得到了模型参数。结果表明:该数学模型能反映解淀粉芽胞杆菌091的细胞生长、底物消耗和抗生素合成的动力学机制,可为该抗真菌抗生素的中试生产提供理论指导。

Fermentation process and kinetics of novel antifungal antibiotic production

A strain Bacillus amyloliquefaciens 091,which shows a strong inhibitory effect against Candida albicans ATCC 64548,was screened from soil samples of East Sea,Zhejiang Province,China.The strain can produce a kind of novel macrolide antibiotic with relative molecular mass 410.In order to increase antibiotic potency,single-factor methodology was applied in the experiment with 250 mL shake flask to optimize the culture conditions.The results are as follows: temperature 28 ℃,initial pH=6.5,rotation speed 200 r/min,inoculation 8%(volume fraction),medium volume 40 mL,and fermentation time 36 h.Under the aforementioned culture conditions,the potency activity of antifungal metabolites is up to 7 026.79 U/mL,which is increased by 2.49 folds compared with that under original culture conditions.According to Logistic,Luedeking-Piret and Luedeking-Piret-like equations,the kinetic models describing cell growth,antifungal metabolites production and substrate consumption were constructed,and the model parameters were fitted by MATLAB software based on the experimental data in 5 L fermentor.The calculation results are in a good agreement with the experimental data and this model can provide the theoretical basis for the antibiotic production in pilot scale.