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Growth-coupled evolution accelerates efficient biosynthesis of natural products
Minjun Chang1, Kyubin Shim1, Dongsoo Yang1
1Synthetic Biology and Enzyme Engineering Laboratory, Department of Chemical and Biological Engineering, Korea University, Seoul 02841, Republic of Korea.
Trends in Biotechnology
|February 15, 2026
Summary
Researchers developed a synthetic feedback loop to boost microbial natural product production. This method links product formation to cell survival, enabling large-scale synthesis and engineering of cell factories.
Area of Science:
- Microbial biotechnology
- Synthetic biology
- Metabolic engineering
Background:
- Microbial natural product biosynthesis is often hindered by metabolic load and genetic instability.
- Developing efficient microbial cell factories for complex natural products remains a challenge.
Purpose of the Study:
- To engineer a synthetic C1 feedback loop to couple xanthommatin production with cell survival.
- To enable adaptive laboratory evolution for enhanced microbial production of natural products.
Main Methods:
- Introduction of a synthetic C1 feedback loop.
- Coupling of xanthommatin production to cell survival.
- Application of adaptive laboratory evolution.
Main Results:
- Achieved gram-scale production of microbial natural products.
- Demonstrated the effectiveness of the synthetic feedback loop strategy.
- Enabled successful adaptive laboratory evolution for enhanced yields.
Conclusions:
- The synthetic C1 feedback loop is a viable strategy for overcoming metabolic burden and genetic instability in microbial biosynthesis.
- This approach provides a generalizable method for engineering cell factories for complex natural product synthesis.
- The study paves the way for improved production of valuable microbial compounds.
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