硫酸盐限制增加了E. coli食批次工艺中的特定等离子体DNA产量和生产率
Mathias Gotsmy1,2, Florian Strobl3, Florian Weiß3
1Department of Analytical Chemistry, University of Vienna, Vienna, 1090, Austria.
Microbial cell factories
|November 29, 2023
概括
优化等离子体DNA (pDNA) 生产包括限制非必需的生长营养素. 在三阶段的料批次过程中,降低硫酸盐的含量可以提高mRNA疫苗的pDNA产量和质量.
科学领域:
- 生物技术是生物技术.
- 代谢工程是代谢工程.
- 制药制造业 制药制造业 制药制造业
背景情况:
- 等离子体DNA (pDNA) 对于mRNA疫苗生产至关重要.
- 标准细胞培养基优化了生长,但可能会限制pDNA产量和质量.
- 为了达到制药生产的高标准,需要平衡细胞生长和产品形成.
研究的目的:
- 使用基于约束的代谢建模优化等离子体DNA (pDNA) 生产.
- 识别支持细胞生长但不支持pDNA复制的介质成分.
- 为了提高pDNA的体积生产率和质量在料批处理过程中.
主要方法:
- 基于约束的代谢建模用于优化.
- 设计了一个三阶段的食批量过程:批量,生长和非生长阶段.
- 使用硫酸盐饥饿诱导过渡到非生长阶段的pDNA生产.
主要成果:
- 确定了一组13种营养素,这些营养素对生长至关重要,但不能复制pDNA.
- 硫酸盐枯竭有效地阻止了细胞生长,增加了pDNA的产生.
- 超卷 pDNA 到生物质的产量增加了33%,体积生产率增加了13%.
结论:
- 对生长介质的简单修改,如硫酸盐限制,可以显著提高pDNA产量和质量.
- 将细胞生长与pDNA生产脱,可以提高制造效率.
- 这一策略提供了一种可行的方法来改进像pDNA这样的常规制造的生物技术产品.
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