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[棘白菌素B高产菌株的构建及发酵调控]

[Construction and fermentation regulation of strains with high yields of echinocandin B].

作者信息

Niu Kun, Cai Hongwei, Ye Yixin, Xu Jinyue, Liu Zhiqiang, Zheng Yuguo

机构信息

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.

出版信息

Sheng Wu Gong Cheng Xue Bao. 2025 Apr 25;41(4):1455-1466. doi: 10.13345/j.cjb.240630.

Abstract

Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of , and its titer in fermentation is significantly affected by the ECB synthesis pathway and cell morphology. In this study, the key genes related to the transcription activation, hydroxylation, and cell morphology during ECB biosynthesis were investigated to increase the fermentation titer of ECB and to change the cell morphology of Aspergillus to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of and , the ECB titer increased by 25.8% and 23.7%, respectively, compared with that of the wild-type strain, reaching (2 030.5±99.2) mg/L and (1 996.4±151.4) mg/L. However, the deletion of associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing was fermented in a 50-L bioreactor, in which the ECB titer reached 2 234.5 mg/L. The findings laid a research foundation for the subsequent metabolic engineering of this strain.

摘要

棘白菌素B(ECB)是抗真菌药物阿尼芬净的关键前体。它是[具体微生物名称]的次生代谢产物,其在发酵中的滴度受ECB合成途径和细胞形态的显著影响。在本研究中,对ECB生物合成过程中与转录激活、羟基化和细胞形态相关的关键基因进行了研究,以提高ECB的发酵滴度,并改变[曲霉菌名称]的细胞形态,降低发酵液的粘度。结果表明,过表达[基因名称1]和[基因名称2]后,与野生型菌株相比,ECB滴度分别提高了25.8%和23.7%,达到(2030.5±99.2)mg/L和(1996.4±151.4)mg/L。然而,与细胞壁合成相关的[基因名称3]的缺失导致细胞壁受损,影响菌株生长和产物合成。过表达[基因名称1]的工程菌株在50-L生物反应器中发酵,其中ECB滴度达到2234.5 mg/L。这些发现为该菌株随后的代谢工程奠定了研究基础。

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