Carbon dioxide (CO₂), as an abundant and renewable carbon feedstock, holds immense potential for sustainable biomanufacturing. However, natural carbon fixation pathways, such as the Calvin-Benson-Bassham (CBB) cycle and the reverse tricarboxylic acid (rTCA) cycle, suffer from intrinsic limitations, including low catalytic efficiency, high adenosine triphosphate (ATP) consumption, and oxygen sensitivity. Recent advances in synthetic biology and metabolic engineering have pioneered artificial pathways (e.g., the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle) that bypass central metabolism, achieving higher fixation rates with reduced ATP consumption. Concurrently, photocatalytic and electrocatalytic systems have emerged as complementary strategies to address cofactor dependency and CO₂ activation thermodynamic barriers. This review summarizes breakthroughs in (ⅰ) rational design for CO₂ conversion pathway optimization, (ⅱ) photocatalysis, and (ⅲ) electrocatalysis for CO₂ activation and cofactor regeneration. By integrating these disciplines, synergistic systems achieve unprecedented efficiency in converting CO₂ to Cn compounds (e.g., ethanol, glyoxylate, sugar, and starch) and establish a foundation for scalable carbon-negative biotechnologies. However, challenges remain, including enzyme denaturation under operational stresses, inefficiencies in multi-enzyme cascades due to kinetic mismatches, and the need for sustainable metrics to ensure net-negative carbon footprints. Future research should prioritize material innovation, CO₂ assimilation system integration, and optimization to unlock higher efficiency CO₂ conversion, aligning with global decarbonization goals while producing high-value chemicals.

Cadaverine is the key monomer for the synthesis of nylon 5X. Efficient and alkaline stable lysine decarboxylases are highly desirable for cadaverine production as the reaction pH increasing from 6.3 to 8.5. However, the most studied lysine decarboxylase CadA (E. coli) lost almost all activity at pH 8.0, which is the foremost challenge for the industrial-cadaverine production. In this study, we first found that the Na⁺-microenvironment significantly improved the alkaline stability of the disulfide engineered lysine decarboxylase ΔLdcEt3 (P233C/L628C) (half-life 362 h), compared to the conventional buffer (half-life 0.66 h) at pH 8.0. Meanwhile, the whole-cell conversion efficiency of the industrial-grade l-lysine with ΔLdcEt3 could reach up to 99% in 2 h in the fermenter. Experimental investigation and molecular dynamics confirmed that Na⁺-microenvironment could improve active-aggregation state and affect secondary structure of ΔLdcEt3. Therefore, Na⁺-microenvironment stabilizes ΔLdcEt3 providing a great potential industrial application for high-level cadaverine production.