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The microorganism\n              <jats:italic>Methanosarcina barkeri<\/jats:italic>\n              is a metabolically versatile methanogen, which can utilize acetate, methanol, and H\n              <jats:sub>2<\/jats:sub>\n              \/CO\n              <jats:sub>2<\/jats:sub>\n              to synthesize methane. However, the regulatory mechanisms underlying methanogenesis for different substrates remain unknown. In this study, RNA-seq analysis was used to investigate\n              <jats:italic>M. barkeri<\/jats:italic>\n              growth and gene transcription under different substrate regimes. According to the results,\n              <jats:italic>M. barkeri<\/jats:italic>\n              showed the best growth under methanol, followed by H\n              <jats:sub>2<\/jats:sub>\n              \/CO\n              <jats:sub>2<\/jats:sub>\n              and acetate, and these findings corresponded well with the observed variations in genes transcription abundance for different substrates. In addition, we identified a novel regulator, MSBRM_RS03855 (designated as HdrR), which specifically activates the transcription of the heterodisulfide reductase\n              <jats:italic>hdrBCA<\/jats:italic>\n              operon in\n              <jats:italic>M. barkeri<\/jats:italic>\n              . HdrR was able to bind to the\n              <jats:italic>hdrBCA<\/jats:italic>\n              operon promoter to regulate transcription. Furthermore, the structural model analyses revealed a helix-turn-helix domain, which is likely involved in DNA binding. Taken together, HdrR serves as a model to reveal how certain regulatory factors control the expression of key enzymes in the methanogenic pathway.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The microorganism\n                <jats:italic>Methanosarcina barkeri<\/jats:italic>\n                has a pivotal role in the global carbon cycle and contributes to global temperature homeostasis. The consequences of biological methanogenesis are far-reaching, including impacts on atmospheric methane and CO\n                <jats:sub>2<\/jats:sub>\n                concentrations, agriculture, energy production, waste treatment, and human health. As such, reducing methane emissions is crucial to meeting set climate goals. The methanogenic activity of certain microorganisms can be drastically reduced by inhibiting the transcription of the\n                <jats:italic>hdrBCA<\/jats:italic>\n                operon, which encodes heterodisulfide reductases. Here, we provide novel insight into the mechanisms regulating\n                <jats:italic>hdrBCA<\/jats:italic>\n                operon transcription in the model methanogen\n                <jats:italic>M. barkeri<\/jats:italic>\n                . The results clarified that HdrR serves as a regulator of heterodisulfide reductase\n                <jats:italic>hdrBCA<\/jats:italic>\n                operon transcription during methanogenesis, which expands our understanding of the unique regulatory mechanisms that govern methanogenesis. The findings presented in this study can further our understanding of how genetic regulation can effectively reduce the methane emissions caused by methanogens.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aem.00691-24","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T13:04:41Z","timestamp":1716987881000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The novel regulator HdrR controls the transcription of the heterodisulfide reductase operon\n            <i>hdrBCA<\/i>\n            in\n            <i>Methanosarcina barkeri<\/i>"],"prefix":"10.1128","volume":"90","author":[{"given":"Sicheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Development and Application of Rural Renewable Energy, Biogas Institute of Ministry of Agriculture and Rural Affairs, Chengdu, 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