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Effects of methyl oleate and microparticle-enhanced cultivation on echinocandin B fermentation titer.
Bioprocess and Biosystems Engineering ( IF 3.8 ) Pub Date : 2020-06-17 , DOI: 10.1007/s00449-020-02389-3
Kun Niu 1, 2 , Xu-Ping Wu 1, 2 , Xiao-Long Hu 1, 2 , Shu-Ping Zou 1, 2 , Zhong-Ce Hu 1, 2 , Zhi-Qiang Liu 1, 2 , Yu-Guo Zheng 1, 2
Affiliation  

Echinocandin B (ECB) is a key precursor of antifungal agent Anidulafungin, which has demonstrated clinical efficacy in patients with invasive candidiasis. In this study, the effects of microparticle-enhanced cultivation and methyl oleate on echinocandin B fermentation titer were investigated. The results showed that the titer was significantly influenced by the morphological type of mycelium, and mycelium pellet was beneficial to improve the titer of this secondary metabolism. First, different carbon sources were chosen for the fermentation, and methyl oleate achieved the highest echinocandin B titer of 2133 ± 50 mg/L, which was two times higher than that of the mannitol. The study further investigated the metabolic process of the fermentation, and the results showed that L-threonine concentration inside the cell could reach 275 mg/L at 168 h with methyl oleate, about 2.5 times higher than that of the mannitol. Therefore, L-threonine may be a key precursor of echinocandin B. In the end, a new method of adding microparticles for improving the mycelial morphology was used, and the addition of talcum powder (20 g/L, diameter of 45 µm) could make the maximum titer of echinocandin B reach 3148 ± 100 mg/L.



中文翻译:

油酸甲酯和微粒增强培养对棘白菌素B发酵效价的影响。

棘白菌素 B (ECB) 是抗真菌剂阿尼芬净的关键前体,已在侵袭性念珠菌病患者中显示出临床疗效。在本研究中,研究了微粒增强培养和油酸甲酯对棘白菌素 B 发酵效价的影响。结果表明,菌丝体形态类型对滴度影响显着,菌丝颗粒有利于提高该次生代谢的滴度。首先,选择不同的碳源进行发酵,油酸甲酯达到了最高的棘白菌素B效价2133±50mg/L,是甘露醇的两倍。该研究进一步研究了发酵的代谢过程,结果表明,油酸甲酯在168h时细胞内L-苏氨酸浓度可达275mg/L,约为甘露醇的2.5倍。因此,L-苏氨酸可能是棘白菌素B的关键前体。使棘白菌素B的最大效价达到3148±100mg/L。

更新日期:2020-06-17
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