The reversible interconversion of formate (HCOO⁻) and carbon dioxide (CO₂) is catalyzed by formate dehydrogenase (FDH, EC 1.17.1.9). This enzyme can be used as a first step in the utilization of CO₂ as carbon substrate for production of high-in-demand chemicals. However, comparison and categorization of the very diverse group of FDH enzymes has received only limited attention. With specific emphasis on FDH catalyzed CO₂ reduction to HCOO⁻, we present a novel classification scheme for FDHs based on protein sequence alignment and gene organization analysis. We show that prokaryotic FDHs can be neatly divided into six meaningful sub-types. These sub-types are discussed in the context of overall structural composition, phylogeny of the gene segment organization, metabolic role, and catalytic properties of the enzymes. Based on the available literature, the influence of electron donor choice on the efficacy of FDH catalyzed CO₂ reduction is quantified and compared. This analysis shows that methyl viologen and hydrogen are several times more potent than NADH as electron donors. Hence, the new FDH classification scheme and the electron donor analysis provide an improved base for developing FDH-facilitated CO₂ reduction as a viable step in the utilization of CO₂ as carbon source for green production of chemicals.

甲酸盐（HCOO的可逆互^- ）和二氧化碳（CO ₂）由甲酸脱氢酶（FDH，EC 1.17.1.9）催化。该酶可以用作利用CO ₂作为生产高需求化学品的碳底物的第一步。但是，非常多样化的FDH酶的比较和分类仅受到了有限的关注。特别强调FDH催化CO ₂还原成HCOO ^-，我们提出了一种基于蛋白质序列比对和基因组织分析的FDHs新分类方案。我们显示原核FDHs可以整齐地分为六个有意义的亚型。在整体结构组成，基因区段组织的系统发育，代谢作用和酶的催化特性的背景下讨论了这些亚型。根据现有的文献，量化和比较了电子供体选择对FDH催化的CO ₂还原效果的影响。该分析表明，作为电子给体，甲基紫精和氢的效能比NADH强几倍。因此，新的FDH分类方案和电子供体分析为开发FDH促进的CO ₂提供了改进的基础。减排是利用CO ₂作为绿色生产化学品的碳源的可行步骤。