Ultrafast Conversion of CO ₂ into C ₃ –C ₄ Diols in a Synergistic Electrochemical and AI-Assisted Biosynthesis System

Using CO₂ as a feedstock to produce high-value chemicals is attractive but remains far from effective in terms of technical application. In particular, efficient conversion of CO₂ into industrially important C₃₊ diols is still challenging. Here, we present a carbon-negative electrochemical-biosynthesis cascade system for synthesizing C₃-C₄ diols (1,3-propanediol, 1,3-PDO, and 1,3-butanediol, 1,3-BDO) directly from CO₂ at exceptionally high productivities. This integrated platform combines a CuZn-catalyzed electrochemical CO₂ reduction reactor operating at Ampere-level current densities (-1,100 mA cm^-2) to produce ethanol (close to 1,200 μmol h^-1 cm^-2) with a biocatalytic module for C-C bond extension. A custom-designed J-T membrane prevents ethanol crossover, enabling accumulation to 4.6 g L^-1 h^-1, while engineered <i>Thermotoga maritima</i> DERA variants (S233D/F43T) exhibit enhanced catalytic efficiency through a synergistic approach combining AI and rational design, achieving a 1,3-PDO production rate of 1.8 g L^-1 h^-1. In situ spectroscopic studies reveal that the presence of key intermediates *CO and *OH, along with the formation of a hydrogen-bonding network, significantly enhances the electrochemical synthesis of ethanol, while molecular dynamics simulations clarify mutation-induced conformational changes in DERA that improve substrate affinity. The system's versatility is further demonstrated by extending ethanol to 1,3-BDO at 1.0 g L^-1 h^-1. This work establishes a scalable paradigm for synthesizing multi-carbon diols from CO₂, bridging the gap between electrocatalysis and synthetic biology for sustainable manufacturing.