Abstract:The Microbial electrosynthesis system (MES) represents a significant interdisciplinary innovation that synergizes microbial reductive metabolism with electrochemical technology. By leveraging the metabolic capabilities of electroactive microorganisms and renewable electricity inputs, MES provides a sustainable platform for converting CO2 into value-added chemicals and mitigating greenhouse gas emissions. Among the various products derived from biological CO2 conversion, acetate has emerged as a key target due to its versatility as a chemical precursor and energy carrier. With applications in food preservation, biopolymer synthesis, and renewable fuel production, acetate holds substantial market value and economic potential, positioning MES as a transformative solution for carbon utilization. At the core of this process lies the reductive acetyl-CoA pathway, commonly known as the Wood-Ljungdahl pathway, a unique metabolic mechanism employed by acetogenic bacteria for efficient CO2 fixation and energy conservation. Unlike conventional CO2 fixation pathways, this pathway allows the direct reduction of CO2 into acetyl-CoA through a series of enzymatic reactions powered by electrons sourced from electrodes or hydrogen. This mechanism achieves high carbon reduction efficiency and offers thermodynamic stability under ambient conditions, making it a cornerstone for scalable CO2-to-acetate conversion. This review examines recent advancements in MES-driven acetate synthesis, with a focus on the optimization of the reductive acetyl-CoA pathway. Optimization strategies are categorized into three areas: (1) Enhancing electron transfer efficiency: The application of nanostructured catalysts has proven effective in accelerating electron transfer to microbial communities, thereby synergistically promoting both indirect and direct electron transfer pathways. (2) Regulating metabolic pathways: Enhancing in situ hydrogen generation and utilization, as well as supplementing with key intermediates such as CO and formate, can significantly improve the conversion of CO2 into value-added products. (3) Integrating CO2 capture and conversion: Coupling MES with advanced adsorbents or gas diffusion electrodes facilitates efficient CO2 mass transfer, addressing solubility limitations in aqueous systems. Finally, future research directions are proposed: (1) Catalyst design driven by machine learning: Integrating experimental data with neural networks could accelerate the identification of optimal electrode materials. (2) Synthetic biology for strain optimization: Applying gene-editing technologies to engineer microbial chassis can significantly enhance electron transfer capacity and improve the efficiency of target product synthesis. (3) System-level sustainability analysis: Life cycle assessments should guide reactor scaling to balance energy inputs with environmental benefits and ensure net-negative carbon emissions. By bridging fundamental insights with engineering innovations, this work provides a comprehensive framework to advance MES from lab-scale prototypes to industrial carbon refineries, ultimately contributing to a circular carbon economy. Close-