Abstract

Methanogenesis is an anaerobic, energy-conserving metabolism that converts CO 2 , acetate, and methylated compounds to methane, constituting a key terminal step in the mineralization of organic matter in many oxygen-limited ecosystems. In the modern biosphere, biological methane formation is overwhelmingly dominated by methanogenic archaea. Despite its phylogenetic constraint, this metabolism exerts disproportionate influence on global carbon cycling, radiative forcing, and methane-based energy systems. The defining biochemical signature of methanogenesis is methyl-coenzyme M reductase (MCR), a nickel tetrapyrrole enzyme that catalyzes the final methane-forming step through Ni-F 430 chemistry. This cofactor chemistry enables selective C-H bond formation and cleavage under aqueous, physiologically compatible conditions. It can also function in the reverse direction in anaerobic methane-oxidizing archaea. This review examines archaeal methanogenesis as a case study in how biochemical constraint and evolutionary diversification jointly shape a single catalytic solution across multiple physiological contexts. We summarize the major routes of methane formation and the bioenergetic architectures that support them. We then evaluate competing scenarios for methanogenesis evolution in light of comparative genomics, geochemical constraints, and the rapidly expanding catalogue of methane-cycling archaea, emphasizing an evolutionary history marked by modular assembly, differential loss, and horizontal transfer rather than a simple pattern of vertical inheritance. Mechanistic sections focus on MCR and related alkyl-coenzyme M reductases, highlighting structural features, cofactor variation, post-translational modification repertoires, and recent advances that illuminate critical steps in Ni-F 430 biosynthesis and ATP-dependent activation of the Ni(I) catalytic state. Finally, we discuss implications for biotechnology and catalysis, including selective methane abatement by mechanism-guided inhibition, strategies to enhance anaerobic digestion and biological biogas upgrading, and the use of MCR family enzymes as experimentally tractable platforms for selective anaerobic hydrocarbon transformations and bioinspired catalyst development.