通过突变发生和过程优化改善Hormonema carpetanum的enfumafungin生产:突变生成和初步的转录组分析
Haodong Chen1, Junyi Wang1, Haolong Huang1
1National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry, Shanghai Institute of Pharmaceutical Industry, Shanghai, 201203, China.
World journal of microbiology & biotechnology
|March 9, 2026
概括
突变酶显著增强了Hormonema carpetanum中的enfumafungin产量,产生了1,621 mg/L. 这一突破解决了抗真菌药物合成的供应限制,改善了可访问性和满足临床需求.
科学领域:
- 微生物学 微生物学
- 生物技术是生物技术.
- 生物化学 生物化学
背景情况:
- 恩法宁是一种重要的抗真菌化合物,用于合成ibrexafungerp和SCY-247.
- 低发酵产量和高生产成本限制了药物的可获得性和临床供应.
研究的目的:
- 为了大规模生产,增强enfumafungin生物合成.
- 通过基因工程识别分子标,以提高恩法因产量.
主要方法:
- 在Hormonema carpetanumATCC 74360.0.的物理和化学突变发生.
- 进行比较的转录组分析以确定上调的途径.
- 优化发酵介质和条件.
- 在5L生物反应器中进行批量发酵.
主要成果:
- 产生了一种高产突变菌,H. carpetanum ENF-5-29,产量为 817 mg/L (增加了 30 倍).
- 转录组分析显示,在低温培养下,恩法因生物合成途径和美酸途径基因的上调调节.
- 优化批量发酵实现了创纪录的1621毫克/升的恩富玛金产量.
结论:
- 突变发生是一种有效的策略,可以改善H. carpetanum.的enfumafungin产量.
- 转录组数据为增强enfumafungin生物合成提供了分子洞察力.
- 该研究确定了未来基因工程的关键目标,以促进恩法林的生产.
更多相关视频
09:42Isolation and Selection of Entomopathogenic Fungi from Soil Samples and Evaluation of Fungal Virulence against Insect Pests
Published on: September 28, 2021
10.7K
10:10Mass Production of Entomopathogenic Fungi, Metarhizium robertsii and Metarhizium pinghaense, for Commercial Application Against Insect Pests
Published on: March 31, 2022
8.4K
相关概念视频
Bioreactor Controls-III
67
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...
67
Production of Antibiotics
265
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...
265
Production of Pharmaceuticals
94
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...
94
