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

Kun NIU; Hongwei CAI; Yixin YE; Jinyue XU; Zhiqiang LIU; Yuguo ZHENG

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

Author: Kun NIU ¹ ; Hongwei CAI ¹ ; Yixin YE ¹ ; Jinyue XU ¹ ; Zhiqiang LIU ¹ ; Yuguo ZHENG ¹
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1. College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
Publication Type:Journal Article
Keywords: Aspergillus nidulans; ecdB overexpression; echinocandin B; regulation of fermentation in a 50-L bioreactor
MeSH: Fermentation; Aspergillus nidulans/genetics*; Echinocandins/genetics*; Bioreactors/microbiology*; Fungal Proteins/biosynthesis*; Metabolic Engineering
From: Chinese Journal of Biotechnology 2025;41(4):1455-1466
CountryChina
Language:Chinese
Abstract: Echinocandin B (ECB) is a key precursor of the antifungal drug anidulafungin. It is a secondary metabolite of Aspergillus nidulans, 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 nidulans to reduce the viscosity of the fermentation broth. The results indicated that after overexpression of ecdB and ecdK, 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 fksA associated with cell wall synthesis resulted in damage to the cell wall, affecting strain growth and product synthesis. The engineered strain overexpressing ecdB 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.