合成微生物联盟的最佳蛋白质生产:共存,劳动的分配和合成
Carlos Martínez1,2, Eugenio Cinquemani3, Hidde de Jong3
1Université Côte d' Azur, Inria, INRAE, CNRS, Sorbonne Université, Biocore Team, Sophia Antipolis, France. carlos.martinez@uv.cl.
Journal of mathematical biology
|July 3, 2023
概括
使用工程Escherichia coli (E. coli) 的合成微生物联盟可以改善重组蛋白质的生产. 最佳策略涉及两种菌株生产蛋白质和参与合成,其中一种菌株的酸盐分泌支持另一种菌株.
科学领域:
- 合成生物学 合成生物学
- 微生物联盟工程的微生物联盟.
- 生物过程优化优化
背景情况:
- 大肠杆菌 (E. coli) 是重组蛋白质生产 (例如生长激素,胰岛素) 的关键宿主.
- 大肠杆菌的溢流代谢导致酸盐分泌,抑制细胞生长并降低蛋白质产量.
- 合成联盟通过结合专门的大肠杆菌菌株提供了一个潜在的解决方案.
研究的目的:
- 开发和分析一个数学模型,用于合成大肠杆菌联盟在一个化学状态.
- 调查两个大肠杆菌菌株稳定共存的条件.
- 为了优化生物工艺性能指标:工艺产量和生产力.
主要方法:
- 两个菌株的大肠杆菌化学定位系统的数学建模.
- 对共存平衡条件的推导.
- 一个多目标优化问题对产量和生产率的数值解决方案.
主要成果:
- 为独特的共存平衡建立了必要和充分的条件.
- 确定了工艺产量和生产率之间的最佳权衡.
- 证明最佳操作需要两种菌株生产重组蛋白质 (而不是分工).
- 显露的缩是必不可少的,其中一种菌株的酸盐分泌支持了另一种菌株的生存.
结论:
- 合成的大肠杆菌联盟可以克服乙酸抑制,提高蛋白质的生产.
- 最佳的性能依赖于集成的动态,包括相互的酸盐交换 (合成).
- 两种菌株的联合生产,而不是严格的劳动分工,最大限度地提高了生物工艺效率.
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