Certain anaerobic microorganisms evolved a mechanism to use H₂ as a reductant in their energy metabolisms. For these purposes, the microorganisms developed H₂-activating enzymes, which are aspirational catalysts in a sustainable hydrogen economy. In the case of the hydrogenotrophic pathway performed by methanogenic archaea, 8e⁻ are extracted from 4H₂ and used as reducing equivalents to convert CO₂ into CH₄. Under standard cultivation conditions, these archaea express [NiFe]-hydrogenases, which are Ni-dependent and Fe-dependent enzymes and heterolytically cleave H₂ into 2H⁺ and 2e⁻, the latter being supplied into the central metabolism. Under Ni-limiting conditions, F₄₂₀-reducing [NiFe]-hydrogenases are downregulated and their functions are predominantly taken over by an upregulated [Fe]-hydrogenase. Unique in biology, this Fe-dependent hydrogenase cleaves H₂ and directly transfers H⁻ to an imidazolium-containing substrate. [Fe]-hydrogenase activates H₂ at an Fe cofactor ligated by two CO molecules, an acyl group, a pyridinol N atom and a cysteine thiolate as the central constituent. This Fe centre has inspired chemists to not only design synthetic mimics to catalytically cleave H₂ in solution but also for incorporation into apo-[Fe]-hydrogenase to give semi-synthetic proteins. This Perspective describes the enzymes involved in hydrogenotrophic methanogenesis, with a focus on those performing the reduction steps. Of these, we describe [Fe]-hydrogenases in detail and cover recent progress in their synthetic modelling.

某些厌氧微生物进化出一种机制，在它们的能量代谢中使用 H ₂作为还原剂。出于这些目的，微生物开发了 H ₂激活酶，它们是可持续氢经济中的理想催化剂。在产甲烷古菌执行的氢营养途径的情况下，8e ^-从4H ₂中提取并用作还原当量以将CO ₂转化为CH ₄。在标准培养条件下，这些古细菌表达 [NiFe]-氢化酶，它们是 Ni 依赖性和 Fe 依赖性酶，并且将 H ₂异裂解为 2H ⁺和 2e ^-，后者被供应到中央代谢。在 Ni 限制条件下，F ₄₂₀还原 [NiFe]-氢化酶被下调，它们的功能主要由上调的 [Fe]-氢化酶接管。这种 Fe 依赖性氢化酶在生物学上是独一无二的，它可以裂解 H ₂并将 H ^-直接转移到含咪唑底物上。[Fe]-氢化酶在由两个 CO 分子、一个酰基、一个吡啶醇 N 原子和作为中心成分的半胱氨酸硫醇盐连接的 Fe 辅助因子处激活 H _{2 。}这个 Fe 中心启发了化学家不仅设计合成模拟物来催化裂解 H ₂在溶液中也可掺入 apo-[Fe]-氢化酶以产生半合成蛋白质。该观点描述了参与氢营养型甲烷生成的酶，重点是那些执行还原步骤的酶。其中，我们详细描述了 [Fe]-氢化酶，并介绍了它们合成模型的最新进展。