Raspberry ketone (RK) is a high-value natural aromatic compound widely used in food, flavors and fragrances, and daily chemical products. Traditional plant extraction methods are constrained by raw material availability and high separation costs, while chemical synthesis suffers from high environmental burden and difficulties in meeting market demand for natural-source products. Biocatalytic synthesis represents the core direction for its green manufacturing. However, existing systems remain limited by bottlenecks such as insufficient enzyme activity and substrate tolerance, poor stability of cofactor regeneration systems, and product titers insufficient for industrial needs. [Objective] To construct an efficient, stable, and scalable biocatalytic synthetic system for RK, overcoming existing technical bottlenecks. [Methods] A flavin-independent ene-reductase from Arabidopsis thaliana, AtQOR, was screened and coupled with formate dehydrogenase from Lactobacillus buchneri, LbFDH, to construct an NADPH self-recycling dual-enzyme cascade system. By optimizing vector copy number and gene expression order, an engineered strain co-expressing both enzymes was constructed, and the optimal strain, Escherichia coli 02, was selected. Key reaction conditions for whole-cell biocatalysis were systematically optimized, and a scale-up experiment was performed in a 1 L fermenter using a fed-batch strategy. The product was quantitatively analyzed and structurally verified using gas chromatography (GC) and nuclear magnetic resonance (NMR) spectroscopy. [Results] The selected AtQOR exhibited a specific activity of 10.35 U/mg in catalyzing the conversion of p-hydroxybenzylidene acetone to RK. Under optimal reaction conditions, E. coli 02 produced 37.88 g/L of raspberry ketone from 40 g/L p‑hydroxybenzylidene acetone in 12 h, with a conversion rate of 93.54%. Using a fed‑batch strategy in a 1 L fermenter, the RK titer reached 54.32 g/L in only 10 h, with a conversion rate of 89.43%, and the product was confirmed to be a high-purity target compound. [Conclusion] The dual-enzyme cascade catalytic system constructed in this study substantially overcomes the existing titer bottleneck in RK biosynthesis, providing an efficient, stable, and scalable technological solution for its industrial green manufacturing.