一个平行生物反应器战略,快速确定生长-合关系的生物生产:一个美瓦隆酸的案例研究
Alec Banner1, Joseph Webb1,2, Nigel Scrutton3
1Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Biotechnology for biofuels and bioproducts
|January 17, 2025
概括
合成生物学使可再生资源的绿色化学品生产成为可能. 这项研究使大肠杆菌能够在没有有毒副产品的情况下高效地产生美酸盐,从而提高了生物制造的可行性.
科学领域:
- 合成生物学和代谢工程用于可持续的化学生产.
- 生物经济的发展,以减少对石化原料的依赖.
- 生物工艺优化用于工业化工制造.
背景情况:
- 气候危机和化石燃料的减少需要在化学制造业中提供绿色替代品.
- 合成生物学提供了从可再生资源中微生物生产化合物的潜力.
- 生物制造产品的商业化是有限的,部分原因是忽视了经济可行性.
研究的目的:
- 开发一种快速评估微生物生长和产品形成关系的方法.
- 为了优化梅瓦酸盐的生产,这是类的关键中间体.
- 为了设计一种微生物菌株,以实现高效且无副产品的美瓦酸盐合成.
主要方法:
- 利用并行生物反应器来绘制生长-合关系 (产品形成率,基质利用率,生长率).
- 在大肠杆菌中使用基因编辑 (ackA-pta操作子和poxB的淘汰) BW25113.
- 使用工业上相关的单位和转换效率量化氨酸生产.
主要成果:
- 在0.34小时-1.1的增长速度下,达到0.18g/g的最大梅瓦诺酸产率系数.
- 鉴定了乙酸作为一种有毒的副产品,抑制了生长和下游加工.
- 工程菌株以最佳速度产生美酸盐,而不会形成乙酸盐.
结论:
- 并行生物反应器对于评估生物过程中的生产力和生长合是有效的.
- 基因工程成功地消除了乙酸副产品,使得有效的美酸盐生产成为可能.
- 在行业相关的指标中报告了甲酸盐产量,提高了早期评估.
相关概念视频
Microbial Growth Measurement: Direct Methods
Direct methods for measuring microbial populations in a culture are essential tools in microbiology, providing quantitative data for various applications. Among these, microscopic counts, plate counts, and serial dilution are widely used techniques, each with unique principles and applications.Microscopic CountsMicroscopic counting involves the use of a Petroff-Hausser chamber, a specialized microscope slide with a grid and defined depth. By observing a liquid culture under a microscope,...
Microbial Growth Measurement: Indirect Methods
Estimating microbial growth is essential for understanding population dynamics and environmental adaptations. Indirect methods provide valuable insights by measuring parameters such as turbidity, metabolic activity, and biomass, enabling efficient and reproducible assessments.During exponential growth, microbial cells scatter light proportionally to their biomass, a principle used in turbidity measurements. About one million cells per milliliter produce detectable scattering, which a...
Bioreactor Design and Operational System
Bioreactors are engineered vessels designed to cultivate microorganisms under controlled conditions for industrial bioprocessing. They maintain sterility and allow precise regulation of pH, temperature, oxygen, and nutrient levels to optimize microbial growth and metabolite production. Bioreactors range from small laboratory units of 1 liter to industrial systems holding up to 500,000 liters, though only about 75% of their volume is actively used for fermentation. The remaining headspace...
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...
Designing Growth Media for Bioreactors
Growth media provide essential nutrients that support cell growth and metabolism, thereby enhancing the yield of valuable products such as enzymes, antibiotics, and biomass. Designing an effective growth medium involves balancing all components to prevent nutrient limitations or toxic excesses, both of which can impair growth and reduce product yields.Composition of a Typical Growth MediumA typical growth medium contains carbon and nitrogen sources, salts, vitamins, trace elements, and...
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...


