Technology-driven revolution in CO₂ fixation: From natural pathways to programmable Biosystems

The escalating atmospheric CO₂ concentration, exceeding 430 ppm since the pre-industrial era, presents a critical threat to global climate stability. Moving beyond mere carbon capture, this review synthesizes cutting-edge advancements in technology-driven CO₂ fixation, focusing on microbial conversion systems. It begins by examining inherent limitations of natural pathways like the Calvin-Benson-Bassham cycle, constrained by low energy efficiency (<1%) and enzymatic inefficiencies of RuBisCO. The discussion then progresses to engineering native pathways and de novo design of synthetic routes (e.g., rGly, CETCH, THETA cycles), which demonstrate superior thermodynamic and kinetic properties for efficient carbon conversion. CRISPR-Cas systems' revolutionary impact, overcoming genetic barriers in carbon-fixing microorganisms. These tools enable precise metabolic rewiring and conversion of heterotrophic chassis into synthetic autotrophs. Furthermore, the convergence of microbiology with electrochemistry and materials science is detailed, highlighting innovative platforms like microbial electrosynthesis and semi-artificial photosynthetic systems. These biohybrid technologies create synergistic interfaces where microbes utilize electrons from electrodes or artificial materials to drive efficient CO₂ reduction into multicarbon compounds, addressing critical energy supply challenges. The review analyzes the transition from natural pathway optimization to custom artificial system construction, underscoring a paradigm shift from isolated improvements to deeply integrated approaches. This new paradigm fuses metabolic engineering, synthetic biology, electrochemistry, and nanomaterials, guided by AI-aided design and modeling. The conclusion emphasizes that seamless integration of microbial capabilities, advanced materials, and artificial intelligence is pivotal for advancing CO₂ fixation toward precision, high efficiency, and carbon negativity, laying the essential foundation for sustainable carbon-negative biomanufacturing and contributing meaningfully to global carbon neutrality goals.