通过Bacillus amyloliquefaciens增强合成S-adenosylmethionine的多层次代谢工程
Cong Jiang1, Dian Zou1, Liying Ruan1
1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, No. 1 Shizishan Street, Hongshan District, Wuhan, 430070, Hubei, People's Republic of China.
Biotechnology letters
|August 20, 2024
概括
基因工程Bacillus amyloliquefaciens的基因工程增强了S-adenosylmethionine (SAM) 的生产. 删除 argG 基因和过度表达 SAM2 基因显著提高了 SAM 产量,达到 452.89 mg/L 的最大标位.
科学领域:
- 微生物学 微生物学
- 代谢工程是代谢工程.
- 合成生物学 合成生物学
背景情况:
- S-adenosylmethionine (SAM) 是一个关键的代谢物,参与了许多细胞甲基化反应.
- 在微生物宿主中增强新的SAM合成对于生物技术应用至关重要.
- 氨酸菌是有价值化合物的工业生产的一个有前途的平台.
研究的目的:
- 为了改善SAM在Bacillus amyloliquefaciens中的新合成.
- 通过模块化策略识别和操纵影响SAM生产的关键基因.
- 为了提高产量,设计一种高SAM产生的菌株.
主要方法:
- 利用模块化策略来检查关键基因对SAM合成的影响.
- 采用基因删除 (argG, moaA) 和基因过度表达 (citA, SAM2) 技术.
- 构建了Bacillus amyloliquefaciens的工程菌株,以提高SAM的生产.
主要成果:
- 删除 argG 基因增加了SAM 标位18%,达到254.78 mg/L.
- 删除 moaA 基因会影响生长,降低 SAM 产量.
- 使用多拷贝等离子体的SAM2基因过度表达导致了最高的SAM标位 (452.89毫克/升).
结论:
- 删除 argG 基因有效地阻止了酸分支降解,增强了 SAM 生产.
- 使用多拷贝等离子体对SAM2基因的过度表达是显著改善SAM合成的最有效策略.
- 改造的Bacillus amyloliquefaciens菌株显示了工业SAM生产的巨大潜力.
更多相关视频
相关概念视频
Synthetic Biology
Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
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...
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 Organic Acids
Lactic acid, an important organic acid extensively applied in food, pharmaceutical, and biodegradable polymer industries, is primarily produced via microbial fermentation. This method is favored over chemical synthesis due to its environmental sustainability and capacity for enantiomerically pure product formation. Among various microbial processes, the fermentation of starch-based substrates stands out due to the abundance and renewability of raw materials like corn and potatoes.Hydrolysis of...
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...


