一种混合的/细胞控制器,可以通过细胞内生物传感处理过程模型不匹配
Tomoki Ohkubo1, Yuichi Sakumura2,3, Fuzhong Zhang4
1Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, 8916-5, Japan. okubo.tomoki.ou1@naist.ac.jp.
Scientific reports
|November 18, 2024
概括
在生物工艺中处理过程模型不匹配的问题是使用混合/细胞控制器 (HISICC) 来解决的. 这种先进的HISICC通过通过细胞内生物传感调节酶水平来改善脂肪酸产量.
科学领域:
- 生物技术是生物技术.
- 合成生物学 合成生物学
- 代谢工程是代谢工程.
背景情况:
- 过程模型不匹配 (PMM) 是优化生物过程的一个重大障碍.
- 此前已经开发了一种混合在/在细胞控制器 (HISICC),以集成基于模型的优化与基于细胞的反.
- 细胞内反机制对于强大的生物过程控制至关重要.
研究的目的:
- 通过细胞内生物传感扩展HISICC方法,通过细胞内生物传感调节关键酶水平.
- 通过解决过程模型不匹配所带来的局限性来加强生物过程控制.
- 通过先进的监管策略,提高工程微生物系统的产量.
主要方法:
- 在工程化大肠杆菌菌株 (FA3) 中实施扩展的HISICC,用于脂肪酸生产.
- 大肠杆菌的基因工程使用反控制器来控制乙-CoA碳酸酶 (ACC) 表达,对马洛尼尔-CoA水平做出反应.
- 对FA3菌株的建模,以使HISICC能够优化诱导器输入的酶表达.
主要成果:
- 模拟表明,HISICC有效地减轻了由PMM引起的快速ACC积累,防止了细胞毒性水平.
- 通过HISICC方法,改造的大肠杆菌中的脂肪酸产量得到了改善.
- 该研究证实了细胞内生物传感在生物过程中管理PMM的有用性.
结论:
- 扩展的HISICC为生物过程优化提供了一个有前途的策略,特别是在处理过程模型不匹配时.
- 细胞内生物传感和反控制对于精确调节酶表达和代谢途径至关重要.
- 这种方法具有显著的潜力,可以提高微生物细胞工厂的效率和产量.
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