Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, P. R. China.
J Appl Microbiol. 2021 Dec;131(6):2849-2860. doi: 10.1111/jam.15136. Epub 2021 May 28.
Echinocandin B (ECB) is a kind of lipopeptide antifungal antibiotic, as well as the key precursor of antifungal drug Anidulafungin. Its efficient bioproduction plays an important role in promoting the industrial production of Anidulafungin.
In this study, methyl oleate and Tween 80 were firstly used to enhance the ECB fermentation by Aspergillus nidulans, the results showed that the ECB titre was significantly enhanced with the addition of methyl oleate and Tween 80. Among the lipids, methyl oleate was found to play a pivotal role in increasing the ECB titre to 2123 mg l , which was more than five times higher than that of the control. The addition of Tween 80 in the medium resulted in ECB titre increased to 2584 mg l . The scanning electron microscope (SEM) and N-phenyl-1-naphthylamine (NPN) assay indicated that Tween 80 could influence the cell membrane permeability of A. nidulans, and enhance the intracellular and extracellular substance exchange, therefore lead to the increasing of ECB titre.
Methyl oleate and Tween 80 are optimal carbon sources and surfactants for efficient ECB biosynthesis respectively.
Surfactant was used in ECB fermentation for the first time, which provided feasible ideas for optimizing the fermentation process of other fungi.
棘白菌素 B(ECB)是一种脂肽类抗真菌抗生素,也是抗真菌药物安尼多fungin 的关键前体。其高效生物合成在促进安尼多fungin 的工业生产中起着重要作用。
本研究首次采用油酸甲酯和吐温 80 来提高构巢曲霉发酵 ECB 的产量,结果表明,添加油酸甲酯和吐温 80 可显著提高 ECB 的产量。在这些脂类物质中,油酸甲酯在提高 ECB 产量方面发挥了关键作用,使 ECB 产量达到 2123mg/L,比对照组提高了五倍以上。在培养基中添加吐温 80 可使 ECB 产量增加到 2584mg/L。扫描电子显微镜(SEM)和 N-苯基-1-萘胺(NPN)测定表明,吐温 80 可以影响构巢曲霉的细胞膜通透性,增强细胞内外物质交换,从而提高 ECB 的产量。
油酸甲酯和吐温 80 分别是 ECB 生物合成的最佳碳源和表面活性剂。
表面活性剂首次用于 ECB 发酵,为优化其他真菌的发酵工艺提供了可行的思路。