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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.

Biotechnology and Bioengineering
|March 30, 2026
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Summary
This summary is machine-generated.

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.

Keywords:
dynamic metabolic controloverflow metabolismprogrammable metabolismsgrT

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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.