Minimal and hybrid hydrogenases are active from archaea.

Microbial hydrogen (H ₂ ) cycling underpins the diversity and functionality of diverse anoxic ecosystems. Among the three evolutionarily distinct hydrogenase superfamilies responsible, [FeFe] hydrogenases were thought to be restricted to bacteria and eukaryotes. Here, we show that anaerobic archaea encode diverse, active, and ancient lineages of [FeFe] hydrogenases through combining analysis of existing and new genomes with extensive biochemical experiments. [FeFe] hydrogenases are encoded by genomes of nine archaeal phyla and expressed by H ₂ -producing Asgard archaeon cultures. We report an ultraminimal hydrogenase in DPANN archaea that binds the catalytic H-cluster and produces H ₂ . Moreover, we identify and characterize remarkable hybrid complexes formed through the fusion of [FeFe] and [NiFe] hydrogenases in ten other archaeal orders. Phylogenetic analysis and structural modeling suggest a deep evolutionary history of hybrid hydrogenases. These findings reveal new metabolic adaptations of archaea, streamlined H ₂ catalysts for biotechnological development, and a surprisingly intertwined evolutionary history between the two major H ₂ -metabolizing enzymes.
Competing Interests: Declaration of interests J.F.B. is a co-founder of Metagenomi. A patent on this discovery and application of ultraminimal hydrogenases was submitted.
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