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新分离的诺卡氏链霉菌突变体对两性霉素B产量的提高

Improvement of amphotericin B production by a newly isolated Streptomyces nodosus mutant.

作者信息

Zhang Bo, Zhang Hai-Dong, Zhou Yi-Teng, Huang Kai, Liu Zhi-Qiang, Zheng Yu-Guo

机构信息

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China.

出版信息

Biotechnol Appl Biochem. 2018 Mar;65(2):188-194. doi: 10.1002/bab.1579. Epub 2017 Oct 2.

Abstract

Amphotericin B is an effective antifungal antibiotic. However, its production in the wild-type strain of Streptomyces nodosus is relatively low. In this study, a strain of ZJB 20130827, capable of producing amphotericin B, was isolated and identified as S. nodosus based on its physiological and biochemical characteristics as well as its 16S rRNA gene sequence analysis. With N-methyl-N-nitroso-N'-nitroguanidine (NTG) and ultraviolet (UV) treatment, this wild-type strain was mutated for improving the yield of amphotericin B. After NTG and UV treatment, the best mutant N3 was obtained for optimization of fermentation conditions. The production of amphotericin B with N3 was 5,260 mg/L, while the wild-type strain ZJB 20130827 was about 580 mg/L, an increase of 906.9%. A genetically stable mutant strain with high yield of amphotericin B was obtained using NTG and UV. The mutant obtained in this work could potentially be utilized in industrial production of amphotericin B.

摘要

两性霉素B是一种有效的抗真菌抗生素。然而,其在诺卡氏链霉菌野生型菌株中的产量相对较低。在本研究中,分离出一株能够产生两性霉素B的菌株ZJB 20130827,并根据其生理生化特性以及16S rRNA基因序列分析将其鉴定为诺卡氏链霉菌。通过N-甲基-N-亚硝基-N'-硝基胍(NTG)和紫外线(UV)处理,对该野生型菌株进行诱变以提高两性霉素B的产量。经过NTG和UV处理后,获得了最佳突变体N3用于发酵条件优化。N3生产两性霉素B的产量为5260 mg/L,而野生型菌株ZJB 20130827约为580 mg/L,提高了906.9%。使用NTG和UV获得了一株遗传稳定的高产两性霉素B突变菌株。本研究中获得的突变体有可能用于两性霉素B的工业生产。

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