Translation of redox biocatalysis into a commercial hydrogenation flow reactor, with in-built electrolytic H2 generation, was achieved using immobilized enzyme systems. Carbon-supported biocatalysts were first tested in batch mode, and were then transferred into continuous flow columns for H2-driven, NADH-dependent asymmetric ketone reductions. The biocatalysts were thus handled comparably to heterogeneous metal catalysts, but operated at room temperature and 1–50 bar H2, highlighting that biocatalytic strategies enable implementation of hydrogenation reactions under mild–moderate conditions. Continuous flow reactions were demonstrated as a strategy for process intensification; high conversions were achieved in short residence times, with a high biocatalyst turnover frequency and productivity. These results show the prospect of using enzymes in reactor infrastructure designed for conventional heterogeneous hydrogenations.

A continuous packed bed reactor for NADH-dependent biocatalysis using enzymes co-immobilized on a simple carbon support was optimized to 100% conversion in a residence time of 30 min. Conversion of pyruvate to lactate was achieved by co-immobilized lactate dehydrogenase and formate dehydrogenase, providing in situ cofactor recycling. Other metrics were also considered as optimization targets, such as low E factors between 2.5–11 and space-time yields of up to 22.9 g L –1 h –1 . The long-term stability of the biocatalytic reactor was also demonstrated, with full conversion maintained over more than 30 h of continuous operation.

Translation of redox biocatalysis into a commercial H-Cube hydrogenation flow reactor was achieved using immobilized enzyme systems for biocatalytic hydrogenations. Carbon-supported enzymes for H2-driven NADH recycling and NADH-dependent C=O reductions were handled comparably to supported metal catalysts. High activity at room temperature with 2 bar H2 was attained, highlighting that biocatalytic strategies enable implementation of hydrogenation reactions under mild conditions. High conversions were achieved in short residence times (< 2 s), with high biocatalyst turnover frequencies (1,420 min-1) and space-time yields (7.9 kg L-1 h-1). These results represent the first example of direct biocatalytic hydrogenation in a commercial flow reactor.

Translation of redox biocatalysis into a commercial H-Cube hydrogenation flow reactor was achieved using immobilized enzyme systems for biocatalytic hydrogenations. Carbon-supported enzymes for H2-driven NADH recycling and NADH-dependent C=O reductions were handled comparably to supported metal catalysts. High activity at room temperature with 2 bar H2 was attained, highlighting that biocatalytic strategies enable implementation of hydrogenation reactions under mild conditions. High conversions were achieved in short residence times (< 2 s), with high biocatalyst turnover frequencies (1,420 min-1) and space-time yields (7.9 kg L-1 h-1). These results represent the first example of direct biocatalytic hydrogenation in a commercial flow reactor.