一种工业性Penicillium citrinum的系统代谢工程,用于一阶段的普拉瓦斯塔丁生产
Mengyi Xiong1, Zhiqiang Du1, Zehao Fan2
1Shandong Provincial Key Laboratory of Synthetic Biology, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, 266101, China; Qingdao New Energy Shandong Laboratory, Qingdao, Shandong, 266101, China; Shandong Energy Institute, Qingdao, Shandong, 266101, China.
Metabolic engineering
|December 18, 2025
概括
研究人员对Penicillium citrinum进行了一步普拉瓦斯塔丁生物合成的工程,提高了效率. 这种新的方法为生产这种降胆固醇药物提供了一种更绿色,更有效的方法.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 工业微生物学 工业微生物学
背景情况:
- 普拉瓦斯塔丁是一种关键的降胆固醇药物,具有有利的特性.
- 目前的工业普拉瓦斯塔丁生产依赖于一种低效的两步发酵过程.
- 使用Streptomyces发酵的第二个生物转化步骤是一个瓶.
研究的目的:
- 为了设计一种工业菌株,以实现高效的一步普拉瓦斯塔丁生物合成.
- 开发一个高性能的细胞工厂,以提高普拉瓦斯塔丁的生产.
- 为了建立一个可持续的和绿色的生产路线为pravastatin.
主要方法:
- 通过整合细胞染色体P450-redox合作伙伴模块进行单步生物合成,通过工程设计的Penicillium citrinum MEFC10.
- 过度表达的NADP+依赖的g6pd3通过NADPH再生来促进他类生物合成.
- 优化了通路转录调节器,自我抵抗基因,并将副产品的形成降至最低,以创建Pra2.0菌株.
主要成果:
- 在Penicillium citrinum中建造了一级普拉瓦斯塔丁生产细胞工厂.
- 在50L生物反应器中开发了一种高性能Pra2.0菌株,在50L生物反应器中达到8.48g/L的普拉瓦斯塔丁和15.06g/L的总他类.
- 与传统方法相比,显著提高了效率.
结论:
- 建立了一个高效的,单步发酵过程,用于生产普拉瓦斯塔丁.
- 开发了一个绿色和可持续的生物合成路径,用于pravastatin.
- 为生产其他复杂的真菌多基菌提供了多功能工程框架.
相关概念视频
Bioreactor Controls-III
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...
Scale-Up Processes
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...
Upstream Processing
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...
Production of Alcohol
Continuous fermentation is a key strategy in industrial ethanol production, particularly when efficiency, scalability, and high yields are essential. This approach allows for uninterrupted operation and optimized resource utilization. The primary feedstock, corn starch, undergoes enzymatic hydrolysis facilitated by α-amylase and glucoamylase. These enzymes break down the starch into fermentable sugars such as glucose, which are readily assimilated by fermentative microorganisms.Fermentation...
Production of Antibiotics
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...
Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...


