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However, the specific minerals reduced, the products formed, and the underlying metabolic mechanisms remain elusive. Here, we report on the cometabolic process of Fe(III) reduction and methylotrophic methanogenesis in\n              <jats:italic>Methanosarcina mazei<\/jats:italic>\n              zm-15. Biogeochemical and mineralogical analyses were conducted to investigate Fe(III) reduction from three mineral preparations\u2014ferrihydrite, goethite, and hematite. The results revealed that 38% of the 6 mM Fe(III) in ferrihydrite was reduced within 4 days, and this percentage increased to 75% with the addition of 100 \u00b5M anthraquinone-2,6-disulfonate (AQDS). Active Fe(III) reduction occurred immediately and preceded rapid methanogenesis. The addition of ferrihydrite and AQDS together significantly enhanced the maximal CH\u2084 production rate. However, Fe(III) reduction did not occur in goethite or hematite, even with the addition of 100 \u00b5M AQDS. Vivianite was identified as the major product from ferrihydrite reduction. Transcriptomic analysis revealed that gene expression related to the oxidation branch of the methyl-dismutating pathway and the membrane-associated electron transport chain (ETC) was significantly upregulated, whereas the expressions of genes associated with the reduction branch of the methyl-dismutating pathway were downregulated. In conclusion,\n              <jats:italic>M. mazei<\/jats:italic>\n              zm-15 demonstrates a strong ability to reduce poorly crystalline ferrihydrite, but not highly crystalline goethite and hematite. During the cometabolism of Fe(III) reduction and CH\u2084 production from methanol, the methyl-oxidation and membrane ETC pathways are enhanced, while the methyl-reduction pathway is downregulated. The mechanism of electron relay from cells to ferrihydrite, however, remains unclear and warrants further investigation.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The recent discovery that certain\n                <jats:italic>Methanosarcina<\/jats:italic>\n                species can grow by reducing Fe(III) challenges the traditional understanding of methanogens. However, the underlying metabolic mechanisms remain largely unexplored. Using a combination of biogeochemical, mineralogical, and microbiological approaches, we investigated the ability of\n                <jats:italic>Methanosarcina mazei<\/jats:italic>\n                zm-15. It exhibited a strong capacity to reduce poorly crystalline ferrihydrite but not highly crystalline goethite and hematite. The formation of vivianite from ferrihydrite reduction is likely due to the high rate of Fe(III) reduction and the presence of excess phosphorus in incubations. During the cometabolism of Fe(III) reduction and CH\n                <jats:sub>4<\/jats:sub>\n                production from methanol, the methyl-oxidation and membrane electron transport pathways are upregulated, while the methyl-reduction pathway is downregulated. Our research uncovers a differential regulation of metabolic pathways during the cometabolism of Fe(III) reduction and CH\n                <jats:sub>4<\/jats:sub>\n                production from methanol. The findings shed new light on the adaptive strategies employed by\n                <jats:italic>M. mazei<\/jats:italic>\n                in environments with the presence of Fe(III) and suggestthat\n                <jats:italic>Methanosarcina<\/jats:italic>\n                can play a significant role in methane production and iron cycling in natural environments.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aem.02238-24","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T14:00:38Z","timestamp":1739455238000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Cometabolism of ferrihydrite reduction and methyl-dismutating methanogenesis by\n            <i>Methanosarcina mazei<\/i>"],"prefix":"10.1128","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0403-2263","authenticated-orcid":false,"given":"Chaojie","family":"Guo","sequence":"first","affiliation":[{"name":"College of Urban and Environmental Science, Peking University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-9868","authenticated-orcid":true,"given":"Yahai","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Urban and Environmental Science, Peking University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41561-021-00715-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.5194\/essd-12-1561-2020"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1155\/2005\/859728"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2017.173"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-041020-024935"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-679"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00939-20"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.033712-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2016.33"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00651-19"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ismejo\/wrae026"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07631-6"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07829-8"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07728-y"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1002-0160(18)60052-9"},{"key":"e_1_3_3_17_2","volume-title":"The prokaryotes","year":"2006","unstructured":"2006. 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