在工程酵母中生产抗疟疾药物前体胺酸
Dae-Kyun Ro1, Eric M Paradise, Mario Ouellet
1California Institute of Quantitative Biomedical Research, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.
Nature
|April 14, 2006
概括
科学家们利用酵母技术制造出艺术氨酸,这是抗疟疾药物艺术氨酸的前体. 这种可持续的微生物生产提供了一种潜在的解决方案来解决甲素短缺和高成本的问题,有助于治疗疟疾.
科学领域:
- 生物技术是生物技术.
- 药用化学 医学化学
- 寄生虫学的寄生虫学
背景情况:
- 疟疾仍然是一个重大的全球健康威胁,每年影响数百万人.
- 抗药性Plasmodium falciparum菌株使疟疾控制工作复杂化.
- 作为一种关键的抗疟疾药物,阿尔特米西宁因提取和合成而面临供应短缺和高成本的挑战.
研究的目的:
- 为了设计Saccharomyces cerevisiae,以经济高效和可持续地生产艺术氨酸,艺术氨酸的前体.
- 开发一种可靠的微生物来源来合成甲美西宁,解决供应的限制.
- 为了通过工程酵母分泌使艺术氨酸更简单地净化.
主要方法:
- 在Saccharomyces cerevisiae中设计了美酸盐路径.
- 引入了阿莫法迪因合成酶和来自Artemisia annua.的新型细胞染色体P450单氧化酶 (CYP71AV1).
- 优化了人工酵母对胺酸的生产和分泌.
主要成果:
- 在工程酵母中达到高位的艺术氨酸 (高达100毫克l(-1))
- 证明合成的艺术氨酸在细胞外分泌和保留,简化了净化过程.
- 与天然植物来源Artemisia annua相比,人工酵母表现出更高的特异性生产率.
结论:
- 微生物生产艺术氨酸是可行的,并为传统艺术氨酸采购提供了一个有前途的替代方案.
- 进一步优化和扩展是必要的,以实现工业可行性和大幅降低基于美素的疗法成本.
- 这种方法可以改善全球获得必要的抗疟疾治疗的机会.
相关概念视频
01:22Bioreactor Controls-III
51
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...
51
01:30Production of Pharmaceuticals
59
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...
59
01:27Production of Antibiotics
67
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...
67
01:25Production of Organic Acids
64
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...
64