优化内生菌株 Fusarium sp. R1 生产 N-甲基香豆素的固定液体发酵条件

Yilan Shao, Yifan Bai, Zhehui Cai, Nan Pu, Huawei Zhang
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摘要

为提高治疗剂 N-甲基沙瓦酰胺(SA)的产量,对内生菌株 Fusarium sp. R1 进行了瓶级固定液发酵条件优化。采用单因素-时间法确定了生产 SA 的发酵条件如下:发酵时间 13 d,温度 24 °C,初始 pH 值 6.5,种龄 24 h,接种量 5.0% (v/v),负载量 50% (v/v),盐度 20.0 g/L。蔗糖、胰蛋白胨和酵母提取物被认为是最佳碳源和氮源。利用响应面方法,最佳培养基成分为 22.5 克/升蔗糖、16.5 克/升胰蛋白胨和 0.024 克/升酵母提取物。验证测试表明,在这些最佳条件下,SA 产量高达 536.77 ± 2.67 mg/L,是初始产量(54.05 ± 3.45 mg/L)的近 10 倍。研究结果表明,在适当的发酵条件下,使用低成本培养基对菌株 R1 进行固定培养,可以获得较高的 SA 产量。这项研究为利用菌株 R1 生产工业规模的 SA 以开发新药物铺平了道路。
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Optimization of Stationary Liquid Fermentation Conditions for N-Methylsansalvamide Production by the Endophytic Strain Fusarium sp. R1
To improve the yield of the therapeutic agent N-methylsansalvamide (SA), optimization of stationary liquid fermentation conditions was conducted on an endophytic strain, Fusarium sp. R1, at flask level. Using a One-Factor-At-a-Time approach, the fermentation conditions for SA production were determined as follows: fermentation time of 13 d, 24 °C, initial pH of 6.5, seed age of 24 h, inoculum size of 5.0% (v/v), loading volume of 50% (v/v), and 20.0 g/L salinity. Sucrose, tryptone, and yeast extract were found to be the best sources of carbon and nitrogen. Using response surface methodology, the optimal medium compositions consisted of 22.5 g/L sucrose, 16.5 g/L tryptone, and 0.024 g/L yeast extract. Verification tests suggested that the SA yield under these optimal conditions reached up to 536.77 ± 2.67 mg/L, which was increased by almost ten times the initial yield (54.05 ± 3.45 mg/L). The findings indicate that a high SA production yield can be achieved by stationary culture of strain R1 under proper fermentation conditions using a low-cost medium. This study paves the way toward industrial-scale SA production by strain R1 for new drug development.
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