{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:03:30Z","timestamp":1785420210940,"version":"3.56.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI19C1352"],"award-info":[{"award-number":["HI19C1352"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00335810"],"award-info":[{"award-number":["RS-2024-00335810"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02214910"],"award-info":[{"award-number":["RS-2025-02214910"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02263193"],"award-info":[{"award-number":["RS-2025-02263193"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Methanotrophs primarily use methane as a carbon and energy source, but they can also grow on methanol. However, methanol assimilation in the absence of methane oxidation results in a redox imbalance due to the accumulation of NADH. In\n                      <jats:italic toggle=\"yes\">Methylomonas<\/jats:italic>\n                      sp. DH-1, a type I methanotroph, we show that this methanol-induced redox stress activates the RegB\/RegA two-component system, a global redox sensor. Methanol triggers the RegB-to-RegA phosphotransfer cascade, resulting in RegA-dependent expression of the\n                      <jats:italic toggle=\"yes\">feo<\/jats:italic>\n                      operon and increased ferrous iron uptake. This iron acquisition is essential for methanol growth, as it supports the function of Na\n                      <jats:sup>+<\/jats:sup>\n                      -transporting NADH:ubiquinone reductase (Na\n                      <jats:sup>+<\/jats:sup>\n                      -NQR), an iron-sulfur cluster-containing enzyme required for NADH oxidation. The operon encoding Na\n                      <jats:sup>+<\/jats:sup>\n                      -NQR complex is upregulated independently of RegA. Together, these findings reveal a redox-sensitive regulatory mechanism in which the RegB\/RegA system senses redox imbalance and promotes iron uptake to facilitate Na\n                      <jats:sup>+<\/jats:sup>\n                      -NQR-mediated NADH reoxidation, thereby restoring redox homeostasis. This study uncovers a critical adaptive strategy for maintaining redox balance during methanol metabolism in methanotrophs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Methanotrophs are emerging as sustainable platforms for converting methane into value-added chemicals. Many species can also utilize methanol\u2014a readily available and industrially attractive alternative\u2014as a carbon source. However, their broader industrial applications have been limited by an incomplete understanding of the fundamental physiological processes that underlie their metabolic and regulatory responses. In this study, we demonstrate how\n                      <jats:italic toggle=\"yes\">Methylomonas<\/jats:italic>\n                      sp. DH-1, an aerobic methanotroph, couples carbon source sensing with redox regulation through the conserved RegB\/RegA two-component system. We show that RegB\/RegA controls iron uptake in response to methanol-induced redox stress, which, in turn, supports NADH reoxidation via Na\u207a-NQR. These findings reveal a redox-responsive regulatory mechanism for methanol utilization and provide a foundation for engineering methanotrophs optimized for methane and methanol bioconversion.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aem.00495-26","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:04:18Z","timestamp":1779195858000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["RegB\/A-dependent redox regulation links iron uptake to methanol metabolism in\n                    <i>Methylomonas<\/i>\n                    sp. DH-1"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8397-1124","authenticated-orcid":false,"given":"Wooyoung","family":"Park","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056tn4839","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5941-5817","authenticated-orcid":true,"given":"Seungwoo","family":"Cha","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056tn4839","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonwoo","family":"Mun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056tn4839","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Lok","family":"Lee","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00saywf64","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology Education, IALS, Gyeongsang National University","place":["JinJu, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7434-7053","authenticated-orcid":true,"given":"Sang Woo","family":"Seo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056tn4839","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-3674","authenticated-orcid":true,"given":"Ji-Sook","family":"Hahn","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/056tn4839","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.4c00519"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.05.008"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-019-1574-9"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-022-02104-2"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0GC02232B"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-024-02557-0"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.9b07414"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2023.129296"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2021.107861"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-022-02105-1"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3CY00737E"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2010.00212.x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.5b00198"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2019.10.004"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-5487-6"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009604"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-78885-2_9"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.68.2.263-279.2004"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01277"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00186"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV120.011188"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2009.11.009"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/jctb.5007"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/catal8030117"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2019.10.002"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-023-02364-6"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509687200"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/md22070299"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.2741\/1232"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2021.111407"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux032"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-023-01099-0"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31718-1"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2024.05.003"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10091377"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.02.017"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad4017"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2017.05.107"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099011"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004837"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000081"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1331021"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-2836(03)00855-6"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101952118"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00043-3"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2016.05.014"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48671-w"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02346062"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1039\/9781788010405-00140"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00762464"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00506-10"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00120-19"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020303"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.00495-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.00495-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:22:47Z","timestamp":1783005767000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aem.00495-26"}},"subtitle":[],"editor":[{"given":"Nicole R.","family":"Buan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,17]]}},"alternative-id":["10.1128\/aem.00495-26"],"URL":"https:\/\/doi.org\/10.1128\/aem.00495-26","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]},"assertion":[{"value":"2026-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00495-26"}}