Woo Seung-Gyun, Kim Seong Keun, Lee Seung-Goo, Lee Dae-Hee
Synthetic Biology Research Center and the K-Biofoundry, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA.
J Biol Eng. 2025 Jan 21;19(1):10. doi: 10.1186/s13036-025-00479-y.
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.
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.
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.
随着我们对肠道微生物群对健康的代谢影响的理解不断加深，对工程益生菌的兴趣也日益浓厚。本研究旨在对益生菌大肠杆菌Nissle 1917（EcN）进行工程改造，使其能够响应肠道炎症生物标志物硫代硫酸盐和硝酸盐产生吲哚乙酸（IAA）。
开发了遗传回路，以便在检测到炎症信号时启动IAA合成，优化异源IAA生物合成途径，并引入RiboJ绝缘子以提高IAA产量。工程改造后的EcN菌株在硫代硫酸盐和硝酸盐存在的情况下，IAA产量有所增加。还开发了一种使用来自恶臭假单胞菌1290的IacR转录因子的IAA响应遗传回路，用于实时监测IAA。
鉴于IAA在减轻胃肠道炎症方面的作用，对该菌株的进一步优化可能会带来有效的、基于IAA的原位治疗方法。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前景的方法。
