Integration of Multiple Enzymes Within Hydrogen‐Bonded Organic Frameworks for Efficient Cascade Photocatalytic CO₂‐to‐Methanol Conversion in Water

The integration of photocatalysts and enzymes within confined environments offers a promising approach to developing artificial photosynthetic systems for sustainable CO2 conversion. However, the efficient coupling of photocatalysts with multiple enzymes to enable photo-enzymatic cascade catalysis remains a significant challenge. Herein, we report the construction of hydrogen-bonded organic frameworks (HOFs) that integrate Ru-based photocatalysts with three-enzyme cascades of formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH), and alcohol dehydrogenase (ADH) via in situ co-assembly in water. The RuHOF exhibits exceptional nicotinamide adenine dinucleotide (NADH) photo-regeneration activity (4.5 mM h-1), while the FDH@RuHOF hybrid converts CO2 to formic acid with a turnover frequency (TOF) of 681 h-1 (238 µM h-1) over 24 h. By engineering FDH/FaldDH/ADH@RuHOF ternary systems, we achieve sustained CO2-to-methanol conversion through photo-enzymatic cascade catalysis, delivering 2.2 mM methanol production with an apparent quantum efficiency (AQY) of 5.5% (92 µM h-1) over 24 h with 85% activity retention after five catalytic cycles. This work opens a promising avenue for the development of efficient multi-enzyme cascade artificial photosynthetic systems toward steady and recyclable CO2 valorization.