{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:16:15Z","timestamp":1792250175181,"version":"4.4.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Intense classical strain improvement has yielded industrial\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Penicillium chrysogenum<\/jats:named-content>\n            strains that produce high titers of penicillin. These strains contain multiple copies of the penicillin biosynthesis cluster encoding the three key enzymes: \u03b4-(l-\u03b1-aminoadipyl)-\n            <jats:sc>l<\/jats:sc>\n            -cysteinyl-\n            <jats:sc>d<\/jats:sc>\n            -valine synthetase (ACVS), isopenicillin N synthase (IPNS), and isopenicillin N acyltransferase (IAT). The phenylacetic acid coenzyme A (CoA) ligase (PCL) gene encoding the enzyme responsible for the activation of the side chain precursor phenylacetic acid is localized elsewhere in the genome in a single copy. Since the protein level of IAT already saturates at low cluster copy numbers, IAT might catalyze a limiting step in high-yielding strains. Here, we show that penicillin production in high-yielding strains can be further improved by the overexpression of IAT while at very high levels of IAT the precursor 6-aminopenicillic acid (6-APA) accumulates. Overproduction of PCL only marginally stimulates penicillin production. These data demonstrate that in high-yielding strains IAT is the limiting factor and that this limitation can be alleviated by a balanced overproduction of this enzyme.\n          <\/jats:p>","DOI":"10.1128\/aem.01529-12","type":"journal-article","created":{"date-parts":[[2012,8,4]],"date-time":"2012-08-04T04:24:53Z","timestamp":1344054293000},"page":"7107-7113","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Increased Penicillin Production in Penicillium chrysogenum Production Strains via Balanced Overexpression of Isopenicillin N Acyltransferase"],"prefix":"10.1128","volume":"78","author":[{"given":"Stefan S.","family":"Weber","sequence":"first","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology, University of Groningen, Zernike Institute for Advanced Materials and Kluyver Centre for Genomics of Industrial Fermentation, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Polli","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology, University of Groningen, Zernike Institute for Advanced Materials and Kluyver Centre for Genomics of Industrial Fermentation, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00ef\u00bf\u00bdmon","family":"Boer","sequence":"additional","affiliation":[{"name":"DSM Biotechnology Center, Delft, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel A. L.","family":"Bovenberg","sequence":"additional","affiliation":[{"name":"DSM Biotechnology Center, Delft, The Netherlands"},{"name":"Synthetic Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology, University of Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold J. M.","family":"Driessen","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology, University of Groningen, Zernike Institute for Advanced Materials and Kluyver Centre for Genomics of Industrial Fermentation, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.46.100192.002333"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18038.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90115-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(00)82098-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.13.6200"},{"key":"e_1_3_2_7_2","first-page":"226","article-title":"The antibacterial action of a Penicillium, with special reference to their use in the isolation of B. influenzae","volume":"10","author":"Fleming A","year":"1929","unstructured":"FlemingA. 1929. 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