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研究报告

阿尼芬净合成前体棘白菌素B发酵条件优化

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  • 浙江工业大学生物工程研究所,浙江杭州310014
牛 坤(1982—),女,山东新泰人,副教授,博士,研究方向为微生物发酵代谢调控,E-mail:niukun@zjut.edu.cn.

基金资助

国家科技重大专项项目(2012YQ15008713)

Optimization of fermentation conditions for Echinocandin B

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  • Institute of Bioengineering,Zhejiang University of Technology,Hangzhou 310014,China

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 237mg/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%.

本文引用格式

牛 坤,吴 豪,毛 健,邹树平 . 阿尼芬净合成前体棘白菌素B发酵条件优化[J]. 发酵科技通讯, 2017 , 46(1) : 11 -15 . DOI: 10.16774/j.cnki.issn.1674-2214.2017.01.004

Abstract

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°C for the
first three days and 25°C for the following nine days,yield of ECB reached 1 237mg/L,which
was 69.9%higher than that cultured at 25°C.The optimal initial pH was 6.5.And the yield of
ECB reached 1 100mg/L by adding 0.6g/L ZnCl2,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 2g/L proline at the 6th days or 2g/L
ornithine at the 3rd days.
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