Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits
Abstract Background As our understanding of gut microbiota’s metabolic impacts on health grows, the interest in engineered probiotics has intensified. This study aimed to engineer the probiotic Escherichia coli Nissle 1917 (EcN) to produce indoleacetic acid (IAA) in response to gut inflammatory biom...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Biological Engineering |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13036-025-00479-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585658841956352 |
|---|---|
| author | Seung-Gyun Woo Seong Keun Kim Seung-Goo Lee Dae-Hee Lee |
| author_facet | Seung-Gyun Woo Seong Keun Kim Seung-Goo Lee Dae-Hee Lee |
| author_sort | Seung-Gyun Woo |
| collection | DOAJ |
| description | Abstract Background As our understanding of gut microbiota’s metabolic impacts on health grows, the interest in engineered probiotics has intensified. This study aimed to engineer the probiotic Escherichia coli Nissle 1917 (EcN) to produce indoleacetic acid (IAA) in response to gut inflammatory biomarkers thiosulfate and nitrate. Results Genetic circuits were developed to initiate IAA synthesis upon detecting inflammatory signals, optimizing a heterologous IAA biosynthetic pathway, and incorporating a RiboJ insulator to enhance IAA production. The engineered EcN strains demonstrated increased IAA production in the presence of thiosulfate and nitrate. An IAA-responsive genetic circuit using the IacR transcription factor from Pseudomonas putida 1290 was also developed for real-time IAA monitoring. Conclusions Given IAA’s role in reducing gastrointestinal inflammation, further refinement of this strain could lead to effective, in situ IAA-based therapies. This proof-of-concept advances the field of live biotherapeutic products and offers a promising approach for targeted therapy in inflammatory bowel diseases. |
| format | Article |
| id | doaj-art-aee88beb963f42528fd981a03f3be2d8 |
| institution | Kabale University |
| issn | 1754-1611 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biological Engineering |
| spelling | doaj-art-aee88beb963f42528fd981a03f3be2d82025-01-26T12:37:29ZengBMCJournal of Biological Engineering1754-16112025-01-0119111210.1186/s13036-025-00479-yEngineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuitsSeung-Gyun Woo0Seong Keun Kim1Seung-Goo Lee2Dae-Hee Lee3Synthetic Biology Research Center and the K-Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Synthetic Biology Research Center and the K-Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Synthetic Biology Research Center and the K-Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Synthetic Biology Research Center and the K-Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB)Abstract Background As our understanding of gut microbiota’s metabolic impacts on health grows, the interest in engineered probiotics has intensified. This study aimed to engineer the probiotic Escherichia coli Nissle 1917 (EcN) to produce indoleacetic acid (IAA) in response to gut inflammatory biomarkers thiosulfate and nitrate. Results Genetic circuits were developed to initiate IAA synthesis upon detecting inflammatory signals, optimizing a heterologous IAA biosynthetic pathway, and incorporating a RiboJ insulator to enhance IAA production. The engineered EcN strains demonstrated increased IAA production in the presence of thiosulfate and nitrate. An IAA-responsive genetic circuit using the IacR transcription factor from Pseudomonas putida 1290 was also developed for real-time IAA monitoring. Conclusions Given IAA’s role in reducing gastrointestinal inflammation, further refinement of this strain could lead to effective, in situ IAA-based therapies. This proof-of-concept advances the field of live biotherapeutic products and offers a promising approach for targeted therapy in inflammatory bowel diseases.https://doi.org/10.1186/s13036-025-00479-yEscherichia coli Nissle 1917Inflammatory bowel diseaseIndoleacetic acidRiboJ insulatorGenetic circuit |
| spellingShingle | Seung-Gyun Woo Seong Keun Kim Seung-Goo Lee Dae-Hee Lee Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits Journal of Biological Engineering Escherichia coli Nissle 1917 Inflammatory bowel disease Indoleacetic acid RiboJ insulator Genetic circuit |
| title | Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits |
| title_full | Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits |
| title_fullStr | Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits |
| title_full_unstemmed | Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits |
| title_short | Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits |
| title_sort | engineering probiotic escherichia coli for inflammation responsive indoleacetic acid production using riboj enhanced genetic circuits |
| topic | Escherichia coli Nissle 1917 Inflammatory bowel disease Indoleacetic acid RiboJ insulator Genetic circuit |
| url | https://doi.org/10.1186/s13036-025-00479-y |
| work_keys_str_mv | AT seunggyunwoo engineeringprobioticescherichiacoliforinflammationresponsiveindoleaceticacidproductionusingribojenhancedgeneticcircuits AT seongkeunkim engineeringprobioticescherichiacoliforinflammationresponsiveindoleaceticacidproductionusingribojenhancedgeneticcircuits AT seunggoolee engineeringprobioticescherichiacoliforinflammationresponsiveindoleaceticacidproductionusingribojenhancedgeneticcircuits AT daeheelee engineeringprobioticescherichiacoliforinflammationresponsiveindoleaceticacidproductionusingribojenhancedgeneticcircuits |