Integration of Multiple Enzymes Within Hydrogen‐Bonded Organic Frameworks for Efficient Cascade Photocatalytic CO 2 ‐to‐Methanol Conversion in Water

Abstract The integration of photocatalysts and enzymes within confined environments offers a promising approach to developing artificial photosynthetic systems for sustainable CO 2 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 CO 2 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 CO 2 ‐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 CO 2 valorization.