通过在指数式养策略下的高细胞密度培养来加强尼古丁胺胺单核酸生产的整体方法
Saroj Raj Kafle1, Anamika Kushwaha1, Lalit Goswami1
1Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
Bioresource technology
|October 23, 2023
概括
尼古丁胺胺单核酸 (NMN) 产量通过在高细胞密度生物反应器中使用工程化大肠杆菌来优化. 这种方法实现了NMN的高产量,NMN是一种具有潜在治疗应用的化合物.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 微生物发酵 微生物发酵
背景情况:
- 尼古丁胺胺单核酸 (NMN) 是一种重要的化合物,具有显著的营养和制药潜力,特别是在与年龄相关的疾病中.
- 现有的NMN生产方法在成本效益和可扩展性方面面临挑战.
- NMN涉及治疗阿尔茨海默病,癌症,衰老和血管功能障碍等疾病.
研究的目的:
- 开发一种有效且可扩展的细胞内NMN生产方法.
- 在高细胞密度生物反应器中使用工程化大肠杆菌菌株来优化NMN产量.
- 建立一个高质量的NMN的成本效益的生产工艺.
主要方法:
- 用于细胞内NMN生产的工程大肠杆菌菌株.
- 高细胞密度生物反应器培养,采用批量养和连续养策略.
- 优化辅基质 (葡萄糖) 和基质 (尼古丁胺胺) 的养特征.
- 液体染色学-质谱学 (LC-MS) 用于NMN量化和验证.
主要成果:
- 达到NMN最大度为19.3g/L,干细胞重量为117g/L.
- 在28小时内从尼古丁胺胺获得98%的高转化效率.
- 通过优化料批发发酵证明了成功的细胞内NMN生产.
- 使用LC-MS分析验证NMN生产.
结论:
- 开发的生物反应器方法使成本高效,高产量和高质量的NMN生产成为可能.
- 这种方法提供了一个可扩展的解决方案,以满足对NMN日益增长的需求.
- 优化微生物发酵为NMN的制药和营养应用提供了一个有前途的战略.
相关概念视频
Inorganic Nitrogen Assimilation
Nitrogen is an essential element in biological systems, forming a crucial component of proteins, nucleic acids, and other cellular constituents. Many bacteria and archaea acquire nitrogen in the form of nitrate (NO₃⁻) or ammonia (NH₃), which are then assimilated into biomolecules through specific enzymatic pathways.Assimilatory Nitrate ReductionWhen nitrate enters the cell, it undergoes a two-step reduction process known as assimilatory nitrate reduction. Initially, the enzyme nitrate reductase...
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...


