在生物生产L-氨酸的挑战和进步
Daniel Alejandro Caballero Cerbon1, Leon Gebhard2, Ruveyda Dokuyucu3
1Chair of Biochemical Engineering, TUM School of Engineering and Design, Technical University of Munich, Boltzmannstraße 15, D-85748 Garching, Germany.
Molecules (Basel, Switzerland)
|January 23, 2024
概括
发酵性生产L-氨酸为传统提取方法提供了一个可持续的替代方案. 代谢工程和过程优化是实现这种重要氨基酸有效的工业规模生物生产的关键.
科学领域:
- 生物技术是生物技术.
- 微生物工程 微生物工程
- 工业微生物学 工业微生物学
背景情况:
- 氨酸是一种重要的氨基酸,具有多种工业应用.
- 传统的从动物来源提取L-氨酸带来了安全和环境问题.
- 使用可再生原料的发酵生产提供了一个可持续的替代方案.
研究的目的:
- 总结了改善微生物宿主用于L-氨酸生物生产的策略.
- 审查新陈代谢工程方法,以提高L-氨酸的产量.
- 概述工业规模发酵生产的工艺工程考虑因素.
主要方法:
- 工程微生物宿主,如 *Pantoea ananatis*, *Corynebacterium glutamicum*, *Pseudomonas* sp. 和 *Escherichia coli*. 这些都是微生物宿主.
- 代谢工程策略包括过度表达反不敏感的酶和L-氨酸输出物,以及削弱降解途径.
- 工艺工程方面,如利用硫酸硫酸盐吸收硫,采用廉价的碳来源,并设计料批次工艺.
主要成果:
- 微生物宿主的成功代谢工程可以显著改善L-氨酸的生产.
- 优化硫的同化和L-氨酸的出口可以提高产量,克服毒性.
- 具有高效净化的可扩展料批处理过程对于工业可行性至关重要.
结论:
- 发酵式L-氨酸生产是一种可行的,可持续的替代动物提取方法.
- 综合代谢和工艺工程方法对于有效的工业规模生物生产至关重要.
- 微生物菌株开发和过程优化的进一步进展将推动生物基L-氨酸的商业化.
相关概念视频
Sulfur Assimilation
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to become...
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...


