Gene Editing-Driven Engineering of Microbial Systems and Metabolites for Precision Medicine and Sustainable Environmental Remediation.

Abstract

The engineering of microorganisms is undergoing a fundamental paradigm shift, transitioning from the construction of static cell factories to the programming of dynamically responsive living materials. However, translating molecular interventions into robust macroscopic functions requires overcoming distinct microbial-specific barriers, including delivery bottlenecks and genetic stability. In this review, we establish a unified Edit-Reprogram-Functionalize conceptual framework that systematically delineates transient genetic regulation from permanent genomic engineering. We critically examine the evolutionary trajectories of five foundational technologies: plasmid engineering, CRISPR-Cas systems, base editors, prime editors, and enzyme engineering. Rather than analyzing these toolsets in isolation, we map their convergence into an integrated engineering continuum that drives the precise synthesis of two distinct output classes: engineered living microbial materials and robust microbial metabolite-derived materials. By evaluating representative breakthroughs-from ultrasound-actuated bacterial therapeutics to ultra-tough, biosynthesized protein composites-through the strict lens of host-dependent constraints, we reveal the mechanistic principles governing successful preclinical translation. Finally, we propose an actionable roadmap centered on systemic miniaturization, closed-loop control, and multi-scale integration, providing a definitive blueprint for the next generation of precision medicine, advanced biomanufacturing, and ecological remediation.