阿尼芬净合成前体棘白菌素B发酵条件优化  

Optimization of fermentation conditions for Echinocandin B

作　　者：牛坤[1] 吴豪[1] 毛健[1] 邹树平[1] 

机构地区：[1]浙江工业大学生物工程研究所,浙江杭州310014

出　　处：《发酵科技通讯》2017年第1期11-15,共5页Bulletin of Fermentation Science and Technology

基　　金：国家科技重大专项项目(2012YQ15008713)

摘　　要：阿尼芬净为新一代棘白菌素类抗生素,其前体物质棘白菌素B(ECB)发酵单位的高低将直接影响阿尼芬净的市场前景.利用构巢曲霉发酵合成ECB,采用单因素实验考察不同参数对ECB产量的影响.结果显示:低温培养有利于ECB的合成,选择前3天37℃培养,后9天25℃培养,ECB产量可达1 237 mg/L,比25℃恒温培养提高了69.9%;最佳的初始pH为6.5;添加0.6g/L ZnCl2可使ECB产量达到1 100mg/L,比初始发酵培养基提高了69.2%;前体物质脯氨酸及鸟氨酸的添加可以显著提高ECB产量,在第6天添加2g/L脯氨酸或在第3天添加2g/L鸟氨酸可使ECB产量分别提高57.4%和55.2%.Anidulafungin is a new echinocandin antifungal agent, and its market prospect is greatly impacted by the fermentation yield of its precursor Echinocandin B （ECB）. ECB was produced by Aspergillus nidulans, and the effect of fermentation conditions on ECB production was investigated by single factor experiment in this paper. The results indicated that lower temperature was in favor of ECB production, and when A. nidulans was cultured at 37℃ for the first three days and 25℃ for the following nine days, yield of ECB reached 1 237 mg/L, which was 69.9% higher than that cultured at 25℃ The optimal initial pH was 6.5. And the yield of ECB reached 1 100 mg/L by adding 0.6 g/L ZnClz, which was 69.2% higher than control. The yield of ECB was enhanced remarkably by addition of proline and ornithine, and it could be improved by 57.4% and 55.2% through the addition of 2 g/L proline at the 6th days or 2 g/L ornithine at the 3rd days.

关 键 词：棘白菌素B 构巢曲霉 发酵 条件优化 

分 类 号：Q92[生物学]