Heterogeneous Catalysis Mediated Cofactor NADH Regeneration for Enzymatic Reduction

Enzymatic reduction using oxidoreductases is important in commercial chemical production. This enzymatic action requires a cofactor (e.g., NADH) as a hydrogen source that is consumed during reaction and must be regenerated. We present, for the first time, an in situ NADH regeneration (NAD+ → NADH) using a heterogeneous catalyst (Pt/Al2O3) and H2 coupled with an enzymatic reduction. This regeneration system can be operated at ambient pressure where NADH yield and turnover frequency (TOF) increased with temperature (20–37 °C) and pH (4.0–9.9) delivering full selectivity to enzymatically active NADH. Cofactor regeneration by heterogeneous catalysis represents a cleaner (H+ as sole byproduct) alternative to current enzymatic and homogeneous (electro- and photo-) catalytic methods with the added benefit of facile catalyst separation. The viability of coupling cofactor regeneration with enzymatic (alcohol dehydrogenase, ADH) reaction is established in aldehyde reduction (propanal to propanol) where 100% alcohol yield was achieved. The potential of this hybrid inorganic–enzymatic system is further demonstrated in the continuous (fed-batch) conversion of propanal with catalyst (activity/selectivity) stability for up to 100 h.