集成放大NADPH再生模块可以增强Escherichia coli中的cytidine生物合成
Lu Liu1, Xiangjun Zhang2, Tengteng Zhu1
1School of Life Science, Ningxia University, Yinchuan, 750021, China.
Synthetic and systems biotechnology
|January 23, 2026
概括
由大肠杆菌 (Escherichia coli) 进行工程改造,通过增强尼古丁胺胺氨酸二核酸盐 (NADPH) 再生来促进细胞胺素的产生. 这种代谢工程策略实现了9.10倍的cytidine标位增加,为生物生产建立了一个新的平台.
科学领域:
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
- 生物技术是生物技术.
背景情况:
- 辅助因子失衡,特别是尼古丁胺胺氨基二核酸盐 (NADPH) 缺乏,限制了大肠杆菌中的酸丁生物合成.
- 解决这种代谢障碍对于有效的微生物生产丁来说至关重要.
研究的目的:
- 为了增强大肠杆菌中NADPH代谢,以增加细胞素的产生.
- 开发一个工程微生物平台,用于高效的cytidine生物生产.
主要方法:
- 利用CRISPR-Cas9多重基因组编辑和构成性促进体替换来增强三个NADPH再生模块 (pntAB,zwf,gnd).
- 在摇瓶中进行发酵,并使用多omics分析分析代谢变化.
主要成果:
- 改造后的NXBG-20菌株获得了7.83g/L的细胞位,比原菌株提高了9.10倍.
- 多omics分析显示,糖解质流向核酸前体的重定向,并增强了ribose-5-phosphate生物合成.
结论:
- 对NADPH新陈代谢的综合工程提供了一个新型的微生物平台,用于cytidine生物生产.
- 这项研究为微生物生产系统的辅助因子驱动的代谢流量控制提供了机制性的见解.
更多相关视频
相关概念视频
Biosynthesis in Bacteria
593
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
593
Biosynthesis of Polysaccharides
581
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
581
Biosynthesis of Lipids
559
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
559
Biosynthesis of Nucleic Acids
1.0K
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
1.0K
Insulin: Biosynthesis, Chemistry, and Preparation
1.3K
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
1.3K
RACE - Rapid Amplification of cDNA Ends
7.2K
Rapid Amplification of cDNA Ends, or RACE, is one of the most effective methods to obtain a full-length cDNA from an mRNA sequence between a known internal region to the unknown sequence at the 5’ or 3’ end. The unknown region is cloned in the cDNA by a gene-specific primer that binds the known end, and a hybrid primer that attaches a predefined anchor sequence to the unknown end of the cDNA. The sequence in between is amplified by PCR with an anchor primer and a gene-specific...
7.2K


