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Genetically Programmed Control of Overflow Metabolism
Lærke M Jensen1, Andriy Glushchuk1, Thilde P Hjorth1
1Department of Biological and Chemical Engineering, Aarhus University, Aarhus, Denmark.
This study presents a novel genetic sensor to detect overflow metabolism in cell factories. The sensor controls glucose uptake, successfully eliminating overflow in batch cultures and significantly reducing it in fed-batch cultures.
Area of Science:
- Metabolic Engineering
- Synthetic Biology
- Biotechnology
Background:
- Overflow metabolism is a persistent challenge in microbial cell factories, limiting productivity.
- Existing strategies to mitigate overflow metabolism have proven insufficient.
Purpose of the Study:
- To design and validate a genetic sensor for detecting overflow metabolism.
- To engineer a system that actively suppresses overflow metabolism in microbial systems.
Main Methods:
- Development of a genetic sensor with demonstrated substrate specificity and reversibility.
- Integration of the sensor with the expression of the SgrT protein.
- Application of the system in E. coli batch and fed-batch cultures.
Main Results:
- The genetic sensor effectively detected overflow metabolism.
- Expression of SgrT successfully inhibited glucose uptake, eliminating overflow in batch cultures.
- Fed-batch cultures showed an 80% reduction in overflow metabolism compared to controls.
Conclusions:
- A novel genetic sensor-based strategy effectively controls overflow metabolism.
- This approach enhances cellular performance and robustness in bioreactor conditions.
- The system offers a promising tool for optimizing industrial microbial processes.
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