An Optimized Bistable Metabolic Switch To Decouple Phenotypic States during Anaerobic Fermentation,ACS Synthetic Biology

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An Optimized Bistable Metabolic Switch To Decouple Phenotypic States during Anaerobic Fermentation
ACS Synthetic Biology ( IF 3.7 ) Pub Date : 2018-10-30 00:00:00 , DOI: 10.1021/acssynbio.8b00284
Naveen Venayak ₁ , Kaushik Raj ₁ , Rohil Jaydeep ₁ , Radhakrishnan Mahadevan _{1,

2}

Affiliation

Metabolic engineers aim to genetically modify microorganisms to improve their ability to produce valuable compounds. Despite the prevalence of growth-coupled production processes, these strategies can significantly limit production rates. Instead, rates can be improved by decoupling and optimizing growth and production independently, and operating with a growth stage followed by a production stage. Here, we implement a bistable transcriptional controller to decouple and switch between these two states. We optimize the controller in anaerobic conditions, typical of industrial fermentations, to ensure stability and tight expression control, while improving switching dynamics. The stability of this controller can be maintained through a simulated seed train scale-up from 5 mL to 500 000 L, indicating industrial feasibility. Finally, we demonstrate a two-stage production process using our optimal construct to improve the instantaneous rate of lactate production by over 50%, motivating the use of these systems in broad metabolic engineering applications.

中文翻译：

优化的双稳态代谢开关，以消除厌氧发酵过程中的表型状态。

代谢工程师的目标是对微生物进行基因改造，以提高其生产有价值的化合物的能力。尽管存在与增长相关的生产过程，但这些策略可能会大大限制生产率。取而代之的是，可以通过独立地分离和优化增长与生产，并在增长阶段然后是生产阶段进行操作来提高生产率。在这里，我们实现了一个双稳态转录控制器，以解耦并在这两个状态之间切换。我们在典型的工业发酵厌氧条件下优化控制器，以确保稳定性和严格的表达控制，同时改善切换动态。该控制器的稳定性可以通过从5 mL到500 000 L的模拟种子培养放大来保持，这表明了工业可行性。最后，

更新日期：2018-10-30

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