{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:50:41Z","timestamp":1790218241244,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Hungarian National Research, Development, and Innovation Fund","award":["K 146406"],"award-info":[{"award-number":["K 146406"]}]},{"name":"Hungarian National Research, Development, and Innovaton Fund","award":["K 138489"],"award-info":[{"award-number":["K 138489"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              For over a century, the filamentous Ascomycete fungus\n              <jats:italic>Aspergillus niger<\/jats:italic>\n              has played a pivotal role in the industrial production of citric acid. A critical fermentation parameter that sustains high-yield citric acid accumulation is the suboptimal concentration of manganese(II) ions in the culture broth at the early stages of the process. However, the requirement for this deficiency has not been investigated on a functional genomics level. In this study, we compared the transcriptome of the citric acid hyper-producer\n              <jats:italic>A. niger<\/jats:italic>\n              NRRL2270 strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn\n              <jats:sup>2+<\/jats:sup>\n              ion-deficient (5 ppb) and Mn\n              <jats:sup>2+<\/jats:sup>\n              ion-sufficient (100 ppb) conditions at three early time points of cultivation. Of the 11,846 genes in the genome, 963 genes (8.1% of the total) were identified as significantly differentially expressed under these conditions. Disproportionately high number of differentially regulated genes encode predicted extracellular and membrane proteins. The most abundant gene group that was upregulated in Mn\n              <jats:sup>2+<\/jats:sup>\n              ion deficiency condition encodes enzymes acting on polysaccharides. In contrast, six clusters of genes encoding secondary metabolites showed downregulation under manganese deficiency. Mn\n              <jats:sup>2+<\/jats:sup>\n              deficiency also triggers upregulation of the\n              <jats:italic>cexA<\/jats:italic>\n              gene, which encodes the citrate exporter. We provide functional evidence that the upregulation of\n              <jats:italic>cexA<\/jats:italic>\n              is caused by the intracellular accumulation of citrate or acetyl-CoA and is a major factor in triggering citrate overflow.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Citric acid is produced on industrial scale by batch fermentation of the filamentous fungus\n              <jats:italic>Aspergillus niger<\/jats:italic>\n              . High-yield citric acid production requires a low (&lt;5 ppb) manganese(II) ion concentration in the culture broth. However, the requirement for this deficiency has not been investigated on a functional genomics level. Here, we compared the transcriptome of a citric acid hyper-producer\n              <jats:italic>A. niger<\/jats:italic>\n              strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn\n              <jats:sup>2+<\/jats:sup>\n              ion-deficient (5 ppb) and Mn\n              <jats:sup>2+<\/jats:sup>\n              ion-sufficient (100 ppb) conditions at three early time points of cultivation. We observed that Mn\n              <jats:sup>2+<\/jats:sup>\n              deficiency triggers an upregulation of the citrate exporter gene cexA and provides functional evidence that this event is responsible for citrate overflow. In addition to the industrial relevance, this is the first study that examined the role of Mn\n              <jats:sup>2+<\/jats:sup>\n              ion deficiency in a heterotrophic eukaryotic cell on a genome-wide scale.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01906-24","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T15:44:11Z","timestamp":1728402251000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomics identify the triggering of citrate export as the key event caused by manganese deficiency in\n            <i>Aspergillus niger<\/i>"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1854-9029","authenticated-orcid":true,"given":"Erzs\u00e9bet","family":"Fekete","sequence":"first","affiliation":[{"name":"Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary"},{"name":"University of Debrecen, Juh\u00e1sz-Nagy P\u00e1l Doctoral School of Biology and Environmental Sciences, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"M\u00e1rton","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary"},{"name":"University of Debrecen, Juh\u00e1sz-Nagy P\u00e1l Doctoral School of Biology and Environmental Sciences, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Bakondi-Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary"},{"name":"University of Debrecen, Juh\u00e1sz-Nagy P\u00e1l Doctoral School of Biology and Environmental Sciences, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzs\u00e9bet","family":"S\u00e1ndor","sequence":"additional","affiliation":[{"name":"Institute of Food Science, Faculty of Agricultural and Food Science and Environmental Management, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Institute of Food Science, Faculty of Agricultural and Food Science and Environmental Management, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Geoffrion","sequence":"additional","affiliation":[{"name":"Centre for Structural and Functional Genomics, Concordia University, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Tsang","sequence":"additional","affiliation":[{"name":"Centre for Structural and Functional Genomics, Concordia University, Montreal, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.","family":"Kubicek","sequence":"additional","affiliation":[{"name":"Institute of Chemical, Environmental and Bioscience Engineering, TU Wien, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Karaffa","sequence":"additional","affiliation":[{"name":"Department of Biochemical Engineering, Faculty of Science and Technology, University of Debrecen, Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/1040841X.2020.1828815"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.56.5.577-585.1948"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.260080402"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-020-1286-7"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00422301"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1985.tb01609.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00408070"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.70.4.2474-2485.2004"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep41040"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.935902"},{"key":"e_1_3_4_12_2","unstructured":"Oliveros JC. 2015. 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