用Bacillus subtilis进行组合代谢工程,以进行de novo的polymyxin B生产
Hui-Zhong Sun1, Qing Li1, Wei Shang1
1Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin, 300350, China.
Metabolic engineering
|April 6, 2024
概括
这项研究工程 Bacillus subtilis 产生polymyxin B,这是一个对抗耐药格兰氏阴性细菌的关键抗生素. 代谢工程显著提升了多素B的产量,达到900mg/L以上.
科学领域:
- 微生物学 微生物学
- 生物技术是生物技术.
- 合成生物学 合成生物学
背景情况:
- 聚米克辛对抗多药耐药格拉姆阴性细菌至关重要,但面临着生产挑战.
- 低位数和同类物存在限制了多素的临床发展.
研究的目的:
- 通过代谢工程来增强多素B的产生和改变其组成.
- 克服聚胺B合成的局限性,并提高其治疗潜力.
主要方法:
- 在Bacillus subtilis中聚胺基因和sfp的异质表达.
- 促进剂,前体合成和非核糖体合成酶 (NRPS) 域的优化.
- 在生物反应器中优化发酵.
主要成果:
- 达到了329.7 mg/L的多素B产量,通过前体合成增强,增加到616.1 mg/L.
- 通过修改NRPS,将多素B1比率从57.5%提高到62.2%.
- 达到962.1 mg/L的最终标位,产量和生产率高.
结论:
- 组合代谢工程成功增强了多素B的产生和B1比率.
- 改造的B. subtilis菌株显示出在工业范围内合成多胺B的巨大潜力.
- 这项工作为开发改进的多素抗生素提供了一个强大的平台.
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