Engineering

Area of Science:

• Synthetic Biology
• Microbial Engineering
• Gastroenterology

Background:

• Uric acid imbalance is linked to chronic diseases, but current monitoring and treatment strategies for hyperuricemia are insufficient.
• Drug therapies for hyperuricemia can cause adverse effects, highlighting the need for alternative management approaches.
• The intestinal tract is crucial for regulating serum uric acid levels, presenting a potential target for therapeutic intervention.

Purpose of the Study:

• To engineer commensal Escherichia coli for the diagnosis and long-term management of hyperuricemia.
• To develop a bioreporter system for detecting uric acid concentration in the intestinal lumen.
• To create a uric acid degradation module for reducing excess uric acid levels.

Main Methods:

• Constructed a bioreporter in E. coli using a synthetic promoter (pucpro) and a uric acid binding protein (PucR).
• Designed a uric acid degradation module overexpressing an E. coli uric acid transporter and B. subtilis urate oxidase.
• Utilized an in vitro Caco-2 cell model to simulate the human intestinal environment for testing engineered E. coli.

Main Results:

• The engineered bioreporter detected uric acid concentration in a dose-dependent manner.
• Engineered E. coli strains degraded 250 µM of uric acid within 24 hours, significantly outperforming wild-type E. coli.
• Engineered E. coli reduced apical uric acid concentration by 40.35% in an in vitro intestinal model.

Conclusions:

• Reprogrammed E. coli demonstrates potential as a synthetic biology therapy for monitoring and maintaining healthy serum uric acid levels.
• Engineered commensal bacteria offer a promising alternative to drug-based treatments for hyperuricemia, minimizing side effects.
• This approach provides a novel strategy for the diagnosis and long-term management of chronic hyperuricemia-related diseases.