一种用于微生物生物工艺的混合in silico/in-cell控制器,该控制器具有工艺模型不匹配的过程
Tomoki Ohkubo1, Yuki Soma2, Yuichi Sakumura1,3
1Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma, Nara, 8916-5, Japan.
Scientific reports
|September 4, 2023
概括
一个新的混合控制系统 (HISICC) 解决了生物工艺中的工艺模型不匹配问题. 它将in silico优化与细胞内反控制器相结合,提高微生物生产效率和可靠性.
科学领域:
- 合成生物学 合成生物学
- 生物工艺工程 生物工艺工程
- 代谢工程是代谢工程.
背景情况:
- 数学模型对于生物过程优化至关重要,但受到了过程模型不匹配 (PMM) 的困扰.
- 模型预测与现实性能之间的这种差异限制了优化效率.
- 现有的方法很难在复杂的生物系统中充分解决PMM问题.
研究的目的:
- 开发和评估一种新的混合在/在细胞控制器 (HISICC) 系统.
- 解决微生物生物工艺中的工艺模型不匹配 (PMM) 的挑战.
- 为了提高异醇 (IPA) 生产在工程Escherichia coli中的优化和可靠性.
主要方法:
- 开发了一种混合控制系统,将一个in silico前控制器与细胞内反控制器集成在一起.
- 使用合成基因电路 (代谢切换开关,细胞密度检测) 的工程大肠杆菌菌株 (TA1415和TA2445).
- 构建并验证了用于优化诱导器 (IPTG) 输入的数学模型,模拟PMM对IPA产量的影响.
主要成果:
- 通过HISICC系统,特别是TA2445菌株,证明了对PMM的有效补偿.
- 细胞内反控制器自主调整了代谢切换开关激活时间.
- 模拟显示了HISICC在细胞生长率中对不同级别的PMM的稳定性,改善了IPA产量.
结论:
- HISICC系统为生物工艺工程中持续存在的PMM问题提供了可行的解决方案.
- 这种方法可以更高效,更可靠地优化微生物生物过程.
- 在工业生物技术领域,HISICC为先进的控制策略铺平了道路.
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