Techno-economic analysis of industrial-scale fermentation for formate dehydrogenase (FDH) production

The conversion of carbon dioxide (CO₂) into formate offers a promising route to enable a circular, carbon-smart bioeconomy. Formate is increasingly recognized as a versatile and energy-dense platform molecule that can serve as a feedstock for microbial fermentation, energy storage, and sustainable chemical and fuel production. A key bottleneck in this value chain is the availability of cost-effective and scalable formate dehydrogenase (FDH), which catalyze the initial reduction of CO₂ to formate. However, little is known about the economic feasibility of producing and purifying FDH at industrial scale. In this study, we developed data-driven techno-economic models to assess the production cost of FDH in Methylorubrum extorquens (M. extorquens) using lab-scale data and projected outcomes across four scenarios: 1 L empirical, 5 L empirical, base, and optimistic. Our results show that the minimum selling price when using FDH as a crude protein preparation ranged from $2300/kg (1 L empirical) to $75/kg (optimistic), while the use of purified FDH resulted in costs ranging from $99,000/kg to $970/kg, respectively. Sensitivity analyses revealed that protein purity has the greatest influence on final production cost, with substrate and electricity costs also contributing significantly to the two empirical scenarios. These findings provide insight into cost bottlenecks and help identify engineering targets for scaling FDH enzyme production, supporting the development of CO₂-to-formate technologies and the broader formate-based bioeconomy.