Glycogen metabolism in methanogens: A key pathway for metabolic response to nutrient availability

Methanogens, which are found exclusively in the Archaea domain of life, have the potential to help solve future energy challenges by producing methane. As a result, their metabolism has attracted significant attention in recent years. Despite being unable to grow on sugars, they store glycogen, which raises intriguing questions about the role of this polymer in methanogen metabolism and the signals that trigger its degradation when methanogenic substrates are not available. Here, we examined genomic databases to identify the enzymes responsible for glycogen synthesis and degradation in methanogens and explored the critical role of glycogen when nutrients and methanogenic substrates are scarce. Additionally, we analyzed the metabolic pathways involved in glycogen metabolism and their connection to the various types of methanogenesis exhibited by these organisms. Potential regulatory steps are proposed based on the reported effectors. Also, by employing the Alphafold3 server, the structural location of these sites in the enzyme structure was predicted, highlighting the advantages and limitations of this tool. Analysis of the allosteric effectors involved in this regulation suggests that energy charge may be the signal that triggers the metabolic switch from gluconeogenesis and glycogen storage to glycolysis and methanogenesis.