The Wolfe cycle of carbon dioxide reduction to methane revisited and the Ralph Stoner Wolfe legacy at 100 years.

Methanogens are a component of anaerobic microbial consortia decomposing biomass to CO₂ and CH₄ that is an essential link in the global carbon cycle. One of two major pathways of methanogenesis involves reduction of the methyl group of acetate to CH₄ with electrons from oxidation of the carbonyl group while the other involves reduction of CO₂ to CH₄ with electrons from H₂ or formate. Pioneering investigations of the CO₂ reduction pathway by Ralph S. Wolfe in the 70s and 80s contributed findings impacting the broader fields of biochemistry and microbiology that directed discovery of the domain Archaea and expanded research on anaerobic microbes for decades that continues to the present. This review presents an historical overview of the CO₂ reduction pathway (Wolfe cycle) with recent developments, and an account of Wolfe's larger and enduring impact on the broad field of biology 100 years after his birth.