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Systems metabolic engineering overcomes bottlenecks for high-level L-cysteine production
Mingli Zhao1, Teng Chen1, Zhaolin Huang1
1State Key Laboratory of Food Science and Resources, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, China.
Metabolic Engineering
|May 17, 2026
Summary
This study engineered Escherichia coli for L-cysteine production by overcoming metabolic bottlenecks. The developed cell factory achieved record-high L-cysteine titer and yield using glycerol as a substrate.
Area of Science:
- Biotechnology
- Metabolic Engineering
- Microbial Engineering
Background:
- L-cysteine is a crucial amino acid for industrial applications.
- Sustainable production is limited by metabolic bottlenecks like regulation, cytotoxicity, and carbon loss.
Purpose of the Study:
- To develop an efficient Escherichia coli cell factory for L-cysteine production.
- To systematically address and resolve interconnected metabolic bottlenecks hindering L-cysteine biosynthesis.
Main Methods:
- Combined multicopy integration and carbon flux redirection for deregulation.
- Identified and resolved 2-hydroxyglutarate accumulation to improve L-serine supply.
- Engineered exporter expression using dynamic regulation and promoter engineering.
Main Results:
- Achieved deregulation and alleviated metabolic burden.
- Overcame L-serine supply bottleneck by resolving toxic accumulation.
- Reduced cytotoxicity and carbon loss through customized exporter expression.
- Demonstrated glycerol superiority over glucose in a 5-L bioreactor, reaching 38.50 g/L titer and 0.17 g/g yield.
Conclusions:
- The developed systematic framework effectively resolves interconnected metabolic bottlenecks.
- This work enables efficient industrial production of L-cysteine through microbial cell factories.
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