高产量和成本效益的生物合成工艺,用于生产抗菌性AA139的抗菌性
Ying Zhang1, Yapeng Wang1, Jianguang Lu2
1School of Pharmacy, Fudan University, Shanghai, 201203, People's Republic of China; Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, People's Republic of China.
Protein expression and purification
|March 29, 2024
概括
这项研究开发了一种新的生物工艺,用于生产AA139,一种强效的抗微生物 (AMP),克服了以前的产量限制. 优化的方法实现了AA139的显著更高的产量,用于对抗耐药细菌的潜在临床应用.
科学领域:
- 生物技术是生物技术.
- 微生物学 微生物学
- 生物化学 生物化学
背景情况:
- AA139是一种强效的抗微生物 (AMP) 变体,对多抗药性 (MDR) 和广泛抗药性 (XDR) 格拉姆阴性细菌表现出活性.
- 以前的AA139生产方法产量低于5mg/L,并且受到复杂化学合成的阻碍,限制了研究和临床使用.
研究的目的:
- 建立一个高效的生物工艺来生产AA139.
- 显著提高复合AA139 (rAA139) 的产量和纯度,以便进一步研究和潜在的临床应用.
主要方法:
- 在使用SUMO融合技术的Escherichia coli (大肠杆菌) BL21 (DE3) 中,AA139在细胞内得到表达.
- 基于物理化学特征,开发了一种简化的下游工艺.
- 高细胞密度发酵 (HCDF) 被优化,以提高54%的蛋白质表达.
主要成果:
- 每升培养物获得56毫克rAA139的产量,纯度为98%,是迄今为止报告的最高产量.
- 鉴定证实了生成的rAA139.9的分子质量,二硫化键和抗菌活性.
- 开发的生物工艺克服了AA139生产的先前局限性.
结论:
- 这项研究提出了一种高效的生物工艺,用于生产重组AA139.
- 这种优化的生产方法显著提高了产量和纯度,促进了AA139作为抗菌剂的未来研究和临床开发.
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