biostudies-literatureDowning BEKinship FoundationU.S. Department of EnergySimons FoundationNational Science Foundation Graduate Research Fellowship ProgramAlfred P. Sloan FoundationNational Institutes of HealthDavid and Lucile Packard FoundationNIH HHSArnold and Mabel Beckman Foundatione0044825https://www.ebi.ac.uk/biostudies/studies/S-EPMC12918732biostudies-literatureUnknown208(2)Methanogenic archaea (methanogens) are microorganisms that obligately produce methane as a byproduct of their energy metabolism. While most methanogens grow on CO₂+H₂, isolates of the genera <i>Methanosarcina</i> and <i>Methanothrix</i> can use acetate as the sole substrate for methanogenesis. Methanogenic growth on acetate, i.e., acetoclastic methanogenesis, is hypothesized to require two distinct genetic modules: one for the activation of acetate to acetyl-CoA and another for producing a chemiosmotic gradient using electrons derived from ferredoxin. In <i>Methanosarcina</i> spp., the activation of acetate to acetyl-CoA is mediated by acetate kinase (Ack) and phosphotransacetylase (Pta), whereas <i>Methanothrix</i> spp. encode AMP-forming acetyl-CoA synthetases (Acs)Journal of bacteriologyGenus-specific remodeling of carbon and energy metabolism facilitates acetoclastic methanogenesis in &lt;i&gt;Methanosarcina&lt;/i&gt; spp. and &lt;i&gt;Methanothrix&lt;/i&gt; spp.PMC12918732Packard Fellowship in Science and Engineering202299857Beckman Young investigator AwardSearle Scholars AwardEarly Career Investigator in Marine Microbial Ecology and EvolutionF32GM150233S589706Sloan Research FellowshipShalvarjian KEDowning BEGupta DNayak DDfalseGenus-specific remodeling of carbon and energy metabolism facilitates acetoclastic methanogenesis in &lt;i&gt;Methanosarcina&lt;/i&gt; spp. and &lt;i&gt;Methanothrix&lt;/i&gt; spp.Methanogenic archaea (methanogens) are microorganisms that obligately produce methane as a byproduct of their energy metabolism. While most methanogens grow on CO₂+H₂, isolates of the genera <i>Methanosarcina</i> and <i>Methanothrix</i> can use acetate as the sole substrate for methanogenesis. Methanogenic growth on acetate, i.e., acetoclastic methanogenesis, is hypothesized to require two distinct genetic modules: one for the activation of acetate to acetyl-CoA and another for producing a chemiosmotic gradient using electrons derived from ferredoxin. In <i>Methanosarcina</i> spp., the activation of acetate to acetyl-CoA is mediated by acetate kinase (Ack) and phosphotransacetylase (Pta), whereas <i>Methanothrix</i> spp. encode AMP-forming acetyl-CoA synthetases (Acs)2026-01-01T00:00:00Z2026 Feb2026-07-16T10:05:15.572Z2026-07-09T10:48:41.41ZS-EPMC129187324156897310.1128/jb.00448-25