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Published on: July 31, 2019
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An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases
Dah Hyun Jung1,2, Ji Hyun Yong1,2, Wontae Hwang1,2
1Department of Microbiology and Immunology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
Journal of Biological Engineering
|March 7, 2021
Summary
Researchers identified novel microbial genes that efficiently convert tributyrin into beneficial butyrate. Engineered E. coli expressing these genes produced butyrate, alleviating colitis symptoms in mice, establishing a targeted delivery system.
Area of Science:
- Microbiology
- Gastroenterology
- Biotechnology
Background:
- Short-chain fatty acids, particularly butyrate, are crucial for gut health.
- Direct butyrate administration faces challenges, prompting interest in prodrugs like tributyrin (TB).
- Tributyrin is a triglyceride precursor that releases butyrate.
Purpose of the Study:
- To identify microbial enzymes capable of hydrolyzing tributyrin into butyrate.
- To develop a system for controlled, in-situ butyrate production in the intestine.
- To evaluate the therapeutic potential of this system in a colitis model.
Main Methods:
- Screening of a mouse microbiome metagenome library (5760 clones) for TB-hydrolyzing activity.
- Identification and sequence analysis of positive clones, including BLASTp for gene homology.
- Expression of candidate genes in Escherichia coli and assessment of butyrate production with TB.
- Evaluation of TB and engineered E. coli in a mouse model of acute colitis.
Main Results:
- Two bacterial clones efficiently hydrolyzed TB into butyrate.
- Homologous genes to acetylesterase/esterase were identified in unknown microbes.
- Proteins contained a conserved catalytic triad (serine-histidine-aspartate).
- E. coli expressing these genes produced significantly more butyrate in the presence of TB.
- Combined administration of TB and engineered E. coli reduced inflammatory symptoms in mice.
Conclusions:
- Novel esterase genes from uncultured microbes enable efficient TB hydrolysis.
- Engineered E. coli can serve as a platform for targeted intestinal butyrate production.
- This approach shows promise for managing inflammatory bowel conditions like colitis.
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