A collaborative research effort by Beijing University of Chemical Technology and Rheinisch-Westfälische Technische Hochschale (RWTH) Aachen has unveiled a novel enzymatic approach for the efficient reduction of C1 compounds, addressing a critical challenge in carbon utilization. Published in Frontiers of Chemical Science and Engineering, the study introduces a hydrogenase-driven coenzyme regeneration method that significantly enhances the sustainability and economic viability of converting greenhouse gases into high-value chemicals.

The reduction of C1 compounds, such as formic acid, is central to carbon dioxide utilization but typically demands substantial energy input, often relying on the expensive coenzyme NADH. Traditional NADH regeneration methods frequently incur high costs and produce undesirable byproducts, limiting their industrial scalability. The new research offers a breakthrough by utilizing hydrogenase, a special biocatalyst capable of regenerating NADH efficiently using renewable hydrogen, without generating byproducts, aligning perfectly with green chemistry principles.

Central to this innovation is the [NiFe]-hydrogenase (SH) derived from Cupriavidus necator, an enzyme distinguished by its excellent oxygen tolerance, making it particularly suitable for industrial environments. The research team constructed a multi-enzyme cascade pathway to demonstrate this concept, converting formic acid into dihydroxyacetone (DHA). In the first step, formaldehyde dehydrogenase (FaldDH) transforms formic acid into formaldehyde, with hydrogenase SH continuously regenerating NADH to power the reaction. Subsequently, formolase (FLS-M3) condenses three formaldehyde molecules into one DHA molecule.

Experimental optimization of hydrogenase heterologous expression conditions enhanced its stability and activity. Thermodynamic calculations initially indicated a high energy barrier for formic acid reduction. However, the continuous supply of NADH by hydrogenase, coupled with the rapid consumption of intermediate formaldehyde by FLS-M3, effectively lowered this barrier, rendering the reaction thermodynamically feasible. The optimized system achieved a DHA accumulation of 373.19 μmol·L⁻¹ within two hours, with a formic acid conversion rate of 7.47%.

This achievement not only validates the efficacy of hydrogen-driven coenzyme regeneration but also demonstrates a novel method for storing low-grade renewable energy, specifically hydrogen, as high-energy-density chemical energy in the form of DHA. The research provides a compelling pathway for carbon dioxide conversion, as formic acid can be electrochemically or photochemically produced from CO2, and DHA can be further processed into various chemicals like alcohols and amino acids, potentially establishing a complete biomanufacturing route from CO2 to valuable products.

While the complex structure of hydrogenase and its mature industrial processes remain challenges, the researchers suggest that techniques such as enzyme immobilization could significantly enhance its stability, promoting future practical applications in cell-free biomanufacturing. This study injects new momentum into green biomanufacturing efforts under global decarbonization initiatives, offering a thermodynamically advantageous route for C1 compound bioconversion.