在Streptomyces中使用插即用系统进行可扩展的二次代谢物生产
Bowen Yang1,2, Zilong Li2,3, Jingyu Zhang1
1State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology (ECUST), Shanghai, China.
Nature biotechnology
|August 15, 2025
概括
一个新的Streptomyces多重化人工控制系统 (SMARTS) 能够精确控制二次代谢物生产. 这个系统成功地扩大了杀虫剂的工业发酵,证明了它在生物技术中的强大应用.
科学领域:
- 微生物学 微生物学
- 合成生物学 合成生物学
- 生物技术是生物技术.
背景情况:
- 菌体物种对于生产具有多种应用的生物活性二次代谢产物至关重要.
- 工业规模的生产需要高效的多目标工程系统来最大限度地提高代谢物产量.
- 现有的方法缺乏统一的方法来控制Streptomyces中多样化的定数感应信号.
研究的目的:
- 开发一种多功能,插即用系统,用于编排Streptomyces中的多目标工程.
- 为了创建一个可以在不同的Streptomyces菌株中应用的定数感应触发式促销器.
- 为增强生产有价值的二次代谢产物而设计菌株.
主要方法:
- 开发了一种基于保存的DNA结合部位的新型定数感应触发式促销器.
- 整合了促进器与稳定器和多重复合模块,创建了Streptomyces多重复合人工控制系统 (SMARTS).
- 工程化Streptomyces avermitilis用于菌素生产和Streptomyces venezuelae用于使用SMARTS生产表素.
主要成果:
- SMARTS将短暂的定数感应信号转换为稳定的多重输出,具有可调节的强度.
- 重新设计的S. avermitilis实现了高度的杀虫剂baiweimectin的生产.
- 成功地将贝维麦生产规模扩大到120立方米的工业发酵,达到8.4g/L.
结论:
- 该SMARTS平台提供了一个强大的和可扩展的解决方案,用于工程Streptomyces.
- 这种系统显著提高了有价值的二次代谢产物的工业生产.
- 在Streptomyces中,SMARTS证明了对本地和异种化合物生产的广泛适用性.
更多相关视频
06:24Generic Protocol for Optimization of Heterologous Protein Production Using Automated Microbioreactor Technology
Published on: December 15, 2017
10.2K
07:59A High-Yield Streptomyces Transcription-Translation Toolkit for Synthetic Biology and Natural Product Applications
Published on: September 10, 2021
4.2K
相关概念视频
01:22Bioreactor Controls-III
54
Strain improvement is a foundational strategy in industrial microbiology aimed at maximizing microbial productivity, particularly because natural isolates typically yield commercially valuable products in very low concentrations. Although optimizing the culture medium and environmental conditions can improve yields, these adjustments are inherently limited by the organism’s genetic potential. As a result, the focus shifts toward genetic modifications to enhance biosynthetic capacity. The...
54
01:14Scale-Up Processes
75
The scale-up of microbial fermentation processes is essential in industrial biotechnology, allowing the transition from laboratory-scale experiments to commercial-scale production while aiming to maintain product yield and quality. This process requires meticulous adjustment of equipment design, process parameters, and contamination control strategies to accommodate increasing culture volumes.At the laboratory scale, cultures are typically maintained in 1 to 10-liter glass or autoclavable...
75
01:27Upstream Processing
80
Upstream processing represents a critical phase in biomanufacturing, wherein biological systems such as microorganisms, mammalian cells, or insect cells are cultivated to produce therapeutic proteins, vaccines, enzymes, or other biologically derived products. This phase encompasses all steps from the selection and genetic manipulation of the production organism to the cultivation of cells in bioreactors under tightly controlled environmental conditions.Host Selection and Genetic OptimizationThe...
80
01:27Production of Antibiotics
84
Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
84