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Orthogonal quorum sensing circuits enable dynamic regulation in Escherichia coli
Michael J Ream1, Kristala L J Prather1
1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Metabolic Engineering
|March 18, 2026
Summary
Engineers used orthogonal quorum sensing (QS) circuits to precisely control gene expression, boosting naringenin production to over 71 mg/L through dynamic metabolic regulation.
Area of Science:
- Synthetic Biology
- Metabolic Engineering
- Microbial Engineering
Background:
- Quorum sensing (QS) is vital for dynamic gene regulation, with acyl homoserine lactones (AHL) widely used.
- AHL-based QS systems often exhibit crosstalk, limiting multi-layered regulatory strategies.
Purpose of the Study:
- To confirm the functional orthogonality of Tra and Rpa QS circuits in Escherichia coli.
- To apply these orthogonal systems for finely-tuned metabolic control in naringenin biosynthesis.
- To optimize dynamic regulation strategies for enhanced compound production.
Main Methods:
- Pairwise interaction analysis of AHL-based QS systems (Tra and Rpa) to confirm orthogonality.
- Application of orthogonal QS circuits to regulate the naringenin biosynthetic pathway.
- CRISPR interference (CRISPRi) for downregulation of competing metabolic pathways.
- Construction of a strain library to screen promoter strengths and AHL induction timings.
Main Results:
- Functional orthogonality of Tra and Rpa QS circuits was confirmed in Escherichia coli MG1655.
- A multi-layered regulatory strategy was successfully implemented for naringenin biosynthesis.
- Optimized dynamic regulation led to a final naringenin titer of 71.02 ± 3.96 mg/L in flask-scale fermentation.
Conclusions:
- Orthogonal QS systems offer precise control for complex metabolic engineering tasks.
- This approach enables combinatorial screening for optimal dynamic regulation strategies.
- The developed autoinducible method significantly enhances target compound production.
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