iDEC 2025 · LZU‑MEDICINE‑CHINA
Intelligent live biotherapeutic for perioperative gut dysbiosis: dual-action precision therapy—barrier repair via oleic acid and pathogen suppression via defensin—coupled with a bile-salt–responsive Hok/Sok biosafety system for gut-specific survival and extra‑intestinal self‑clearance.
Highlights
Dual‑Action Therapeutic Design
Metabolic module secretes oleic acid for barrier repair; immune module expresses defensin to clear pathogens—two synergistic pathways.
Signal‑Coupled Biosafety
P16090 bile‑salt responsive promoter couples therapy with Hok/Sok: suppressed toxin in‑gut, rapid self‑lysis outside.
Reproducible Experiments
Systematic experimental design and documentation with complete results for verification and extension.
Modular Circuits
Therapy, sensing, and safety modules decoupled for flexible composition across hosts and scenarios.
Human‑Centric Practices
Education, inclusivity, and sustainability initiatives aligned with clinical needs and social impact.
Open & Standardized
Complete documentation, reusable parts, and standardized records to foster open collaboration.
Project Overview
Perioperative gut dysbiosis is prevalent and lacks standardized therapies. We engineer an intelligent probiotic that, under gut‑specific signals, executes two coordinated therapeutic functions: secreting oleic acid to repair the barrier and expressing defensin to suppress pathogens and strengthen immune defense.
These therapeutic circuits are coupled to a bile‑salt signal–regulated Hok/Sok biosafety system to fundamentally address the risk of environmental escape: active and therapeutic in the gut, self‑clearing outside, enabling precise spatial control.
Core Parts
| Part Name | Type | Description |
|---|---|---|
| BBa_25CA4F5T | Coding | Encodes stearoyl-CoA 9-desaturase (OLE1), catalyzes stearic acid to oleic acid; codon-optimized for L. lactis. |
| BBa_25ZF6KGL | Coding | Encodes accA, enhances fatty acid synthesis, increases short-chain fatty acids for oleic acid production. |
| BBa_25S2TG5Z | Promoter | Bile salt-responsive promoter (P16090) from Lactobacillus, regulates gene expression in response to bile salts. |
| BBa_25VPY4CG | Coding | Encodes defensin DEFB4A, antimicrobial peptide from human genome, expressed in engineered bacteria. |
| BBa_25NBMOAR | Measurement | Synthetic sequence (P16090-RBS-OLE1-2AA-DEFB4A-Terminator), enables bile salt-induced expression of OLE1/DEFB4A. |
| BBa_251CFLR3 | Plasmid | Plasmid backbone PIP501 from Enterococcus faecium, used for biosafety system construction in various microorganisms. |