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Citric acid overflow requires Mn(II) ion concentrations not exceeding 5\u00a0\u00b5g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      . However, manganese easily leaches from media ingredients or stainless-steel bioreactors, necessitating costly, laborious removal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Aspergillus niger<\/jats:italic>\n                      citrate fermentations were evaluated across varied manganese profiles, comparing a novel double transporter mutant against parental and single-mutant strains. This strain overexpresses\n                      <jats:italic>cexA<\/jats:italic>\n                      \u2013 the primary plasma membrane exporter whose activity overcomes a major production bottleneck \u2013 under the control of the strong\n                      <jats:italic>glaA<\/jats:italic>\n                      promoter in a background deficient in\n                      <jats:italic>dmtA<\/jats:italic>\n                      , which encodes the primary high-affinity NRAMP-family manganese transporter. Under high-manganese conditions (100\u2013165\u00a0\u00b5g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      ) simulating industrial substrate impurities and bioreactor leaching, the double transporter mutant outperformed the other strains. Despite abundant manganese that triggers high biomass (50\u00a0g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      ) and low citrate yields in the parental strain NRRL2270, this cell factory maintained high-yield overflow metabolism. Driven by an accelerated maximal glucose consumption rate of 1.61\u00a0g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      h\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      and reduced biomass accumulation (9.1\u00a0g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      ), it accumulated citric acid to levels comparable to those achieved under manganese deficiency. The double transporter mutant compressed the fermentation period by 17% (from 300 to 250\u00a0h), minimizing operational energy and utility costs and significantly enhancing overall productivity. To validate industrial scalability, the untreated, high-manganese process was replicated in 15-L stainless steel bioreactors \u2013 accounting for up to 30\u00a0\u00b5g L\n                      <jats:sup>\u2212\u20091<\/jats:sup>\n                      of manganese leaching \u2013 and successfully scaled up by an order of magnitude in a 150-L bioreactor. Carbon balance closures within \u00b1\u20095% confirmed no appreciable by-product formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      By demonstrating the maintenance of high-yield overflow metabolism under manganese-replete conditions, alongside enhanced productivity through shortened fermentation times across different vessel scales, this study establishes this\n                      <jats:italic>A. niger<\/jats:italic>\n                      mutant as an attractive cell factory for industrial applications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12934-026-03082-y","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T12:48:24Z","timestamp":1786020504000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eliminating manganese sensitivity and boosting citric acid production in Aspergillus niger through transporters manipulation"],"prefix":"10.1186","volume":"25","author":[{"given":"Alexandra","family":"M\u00e1rton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josee","family":"Vandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzs\u00e9bet","family":"Fekete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzs\u00e9bet","family":"S\u00e1ndor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9la","family":"Kov\u00e1cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Tsang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Karaffa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"3082_CR1","first-page":"1652","volume-title":"Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology 3","author":"CP Kubicek","year":"2010","unstructured":"Kubicek CP, Karaffa L. 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