Engineering probiotic Escherichia coli for inflammation-responsive indoleacetic acid production using RiboJ-enhanced genetic circuits.

IF 5.7 3区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Biological Engineering Pub Date : 2025-01-21 DOI:10.1186/s13036-025-00479-y

Seung-Gyun Woo, Seong Keun Kim, Seung-Goo Lee, Dae-Hee Lee

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引用次数: 0

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.

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工程益生菌大肠杆菌用于炎症反应性吲哚乙酸生产利用核糖酶增强基因回路。

背景：随着我们对肠道菌群代谢对健康影响的了解不断加深，对工程益生菌的兴趣也日益浓厚。本研究旨在设计益生菌大肠杆菌Nissle 1917 （EcN）产生吲哚乙酸（IAA），以响应肠道炎症生物标志物硫代硫酸盐和硝酸盐。结果：在检测到炎症信号的情况下，建立了启动IAA合成的遗传回路，优化了异种IAA生物合成途径，并加入了RiboJ绝缘子来增强IAA的产生。工程EcN菌株在硫代硫酸盐和硝酸盐的存在下显示出IAA产量增加。利用恶臭假单胞菌1290的IacR转录因子构建了IAA响应遗传回路，用于实时监测IAA。结论：考虑到IAA在减少胃肠道炎症中的作用，进一步改进该菌株可能会导致有效的，基于IAA的原位治疗。这一概念验证推动了活体生物治疗产品领域的发展，并为炎症性肠病的靶向治疗提供了一种有希望的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Biological Engineering BIOCHEMICAL RESEARCH METHODS-BIOTECHNOLOGY & APPLIED MICROBIOLOGY

CiteScore

7.10

自引率

1.80%

发文量

审稿时长

17 weeks

期刊介绍： Biological engineering is an emerging discipline that encompasses engineering theory and practice connected to and derived from the science of biology, just as mechanical engineering and electrical engineering are rooted in physics and chemical engineering in chemistry. Topical areas include, but are not limited to: Synthetic biology and cellular design Biomolecular, cellular and tissue engineering Bioproduction and metabolic engineering Biosensors Ecological and environmental engineering Biological engineering education and the biodesign process As the official journal of the Institute of Biological Engineering, Journal of Biological Engineering provides a home for the continuum from biological information science, molecules and cells, product formation, wastes and remediation, and educational advances in curriculum content and pedagogy at the undergraduate and graduate-levels. Manuscripts should explore commonalities with other fields of application by providing some discussion of the broader context of the work and how it connects to other areas within the field.