A bacterial transcription activator dedicated to the expression of the enzyme catalyzing the first committed step in fatty acid biosynthesis

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dc.citation.firstpage12930en_US
dc.citation.issueNumber21en_US
dc.citation.journalTitleNucleic Acids Researchen_US
dc.citation.lastpage12944en_US
dc.citation.volumeNumber52en_US
dc.contributor.authorXu, Yuanyouen_US
dc.contributor.authorLin, Zihanen_US
dc.contributor.authorHou, Jiyuanen_US
dc.contributor.authorYe, Kaien_US
dc.contributor.authorHan, Siruien_US
dc.contributor.authorLiang, Yuxuanen_US
dc.contributor.authorLiang, Huihuien_US
dc.contributor.authorWu, Shihuaen_US
dc.contributor.authorTao, Yizhi Jen_US
dc.contributor.authorGao, Haichunen_US
dc.date.accessioned2025-01-09T20:17:02Zen_US
dc.date.available2025-01-09T20:17:02Zen_US
dc.date.issued2024en_US
dc.description.abstractAcetyl-CoA carboxylase (ACCase) catalyzes the first committed and rate-limiting step of de novo fatty acid synthesis (FAS). Although this step is tightly regulated, regulators that specifically control transcription of the ACCase genes remain elusive. In this study, we identified LysR-type transcriptional regulator AccR as a dedicated activator for the transcription of accS, a gene encoding a multiple-domain ACCase in Shewanella oneidensis. We showed that AccR interacts with the accS promoter in vivo in response to changes in acetyl-CoA levels and in vitro. Analysis of the crystal structure of the effector-binding domain (EBD) of AccR identified two potential ligand-binding pockets, one of which is likely to bind acetyl-CoA as a ligand based on results from molecular docking, direct binding assay and mutational analysis of the residues predicted to interact with acetyl-CoA. Despite this, the interaction between AccR and acetyl-CoA alone appears unstable, implying that an additional yet unknown ligand is required for activation of AccR. Furthermore, we showed that AccR is acetylated, but the modification may not be critical for sensing acetyl-CoA. Overall, our data substantiate the existence of a dedicated transcriptional regulator for ACCases, expanding our current understanding of the regulation of FAS.en_US
dc.identifier.citationXu, Y., Lin, Z., Hou, J., Ye, K., Han, S., Liang, Y., Liang, H., Wu, S., Tao, Y. J., & Gao, H. (2024). A bacterial transcription activator dedicated to the expression of the enzyme catalyzing the first committed step in fatty acid biosynthesis. Nucleic Acids Research, 52(21), 12930–12944. https://doi.org/10.1093/nar/gkae960en_US
dc.identifier.digitalgkae960en_US
dc.identifier.doihttps://doi.org/10.1093/nar/gkae960en_US
dc.identifier.urihttps://hdl.handle.net/1911/118131en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleA bacterial transcription activator dedicated to the expression of the enzyme catalyzing the first committed step in fatty acid biosynthesisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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