F ₄₂₀ reduction as a cellular driver for anaerobic ethanotrophy

The anaerobic ethane oxidation performed by seafloor archaea and sulfate-reducing partner bacteria involves largely uncharted biochemistry. This study deciphers the molecular basis of the CO ₂ -generating steps by characterizing the native archaeal enzymes isolated from a thermophilic enrichment culture. While other microorganisms couple these steps to ferredoxin reduction, we found that the CO-dehydrogenase and the formylmethanofuran-dehydrogenase are bound to an F ₄₂₀ -reductase module. The crystal structures of these multi-metalloenzyme complexes revealed a [4Fe-4S]-cluster networks electronic bridges coupling C1-oxidation to F ₄₂₀ -reduction. Accordingly, both systems exhibit robust F ₄₂₀ -reductase activities, which are not detected in methanogenic or methanotrophic relative organisms. We speculate that the whole catabolism of these archaea is reoriented towards F ₄₂₀ -reduction, which facilitates the electron transfer to the sulfate-reducing partner, therefore representing the driving force of ethanotrophy.