Abstract:Microbial electrosynthesis system (MES) represents a groundbreaking interdisciplinary innovation that synergizes microbial reductive metabolism with electrochemical technology. By leveraging the metabolic capabilities of electroactive microorganisms and renewable electricity inputs, MES offers a sustainable platform for converting CO2 into value-added chemicals and mitigating greenhouse gas emissions. Among the diverse products derived from biological CO2 conversion, acetate has emerged as a pivotal target due to its versatility as a chemical precursor and energy carrier. With applications spanning 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 distinctive metabolic mechanism utilized by acetogenic bacteria for efficient CO2 fixation and energy conservation. Unlike conventional CO2 fixation pathways, this pathway enables the direct reduction of CO2 into acetyl-CoA through a series of enzymatic reactions powered by electrons sourced from electrodes or H2. This mechanism achieves high carbon reduction efficiency and ensures 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 enhancing the reductive acetyl-CoA pathway. Optimization strategies are categorized into three areas: (1) Enhancing electron transfer efficiency: The application of nanostructured catalysts has demonstrated significant effectiveness in enhancing the rate of electron transfer to microbial communities, thereby promoting both indirect and direct electron transfer pathways synergistically. (2) Regulating metabolic pathways: Enhancing the in-situ generation and utilization of hydrogen, and introducing key intermediates involved in the reductive acetyl-CoA pathway, such as CO and formate, can significantly facilitate the conversion of CO2 into value-added products. (3) CO2 capture-conversion integration: Coupling MES with advanced adsorbents or gas diffusion electrodes ensures efficient CO2 mass transfer, addressing solubility limitations in aqueous systems. Finally, future research directions are proposed: (1) Machine learning-driven catalyst design: Integrating experimentation with neural networks could rapidly identify optimal electrode materials. (2) Synthetic biology for strain optimization: Applying gene editing technologies to engineer microbial chassis can significantly enhance electron transfer capacity and facilitate the efficient synthesis of target products. (3) System-level sustainability analysis: Life cycle assessments should guide reactor scaling to balance energy inputs with environmental benefits to ensure net-negative carbon emissions. By bridging fundamental insights with engineering innovations, this work provides a holistic framework to advance MES from lab-scale prototypes to industrial carbon refineries, ultimately contributing to a circular carbon economy. Close-