Methanogens are a diverse group of archaea with ancient evolutionary origins. They are found in a wide range of anoxic environments where they carry out a form of anaerobic respiration known as methanogenesis. This process reduces simple oxidized carbon compounds to generate methane as an end product. Another group of archaea related to methanogens carry out the anaerobic oxidation of methane (AOM) and are known as anaerobic methanotrophs (ANME). Methanogens and ANME are both key components in the global carbon cycle and play a central role in controlling atmospheric methane concentrations. Consistent with their anaerobic lifestyles and ancient evolutionary origins, methanogens and ANME contain an abundance of Fe-S cluster proteins. Radical S-adenosylmethionine (SAM) enzymes are [4Fe-4S]-cluster containing enzymes that catalyze a wide variety of difficult biochemical reactions through the generation of a highly reactive 5’-deoxyadenosyl radical. Here, we discuss our recent progress towards uncovering the functions of novel radical SAM enzymes in methanogens and ANME. We identified the missing glutamate 2,3-aminomutase important for salt tolerance in marine organisms as well as characterized the first archaeal methylthiotransferase involved in tRNA modification.
