{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:26:57Z","timestamp":1790717217938,"version":"4.1.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"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":[[2010,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Industrial penicillin production levels by the filamentous fungus\n            <jats:italic>Penicillium chrysogenum<\/jats:italic>\n            increased dramatically by classical strain improvement. High-yielding strains contain multiple copies of the penicillin biosynthetic gene cluster that encodes three key enzymes of the \u03b2-lactam biosynthetic pathway. We have analyzed the gene cluster dose effect on penicillin production using the high-yielding\n            <jats:italic>P. chrysogenum<\/jats:italic>\n            strain DS17690 that was cured from its native clusters. The amount of penicillin V produced increased with the penicillin biosynthetic gene cluster number but was saturated at high copy numbers. Likewise, transcript levels of the biosynthetic genes\n            <jats:italic>pcbAB<\/jats:italic>\n            [\u03b4-(\n            <jats:sc>l<\/jats:sc>\n            -\u03b1-aminoadipyl)-\n            <jats:sc>l<\/jats:sc>\n            -cysteinyl-\n            <jats:sc>d<\/jats:sc>\n            -valine synthetase],\n            <jats:italic>pcbC<\/jats:italic>\n            (isopenicillin N synthase), and\n            <jats:italic>penDE<\/jats:italic>\n            (acyltransferase) correlated with the cluster copy number. Remarkably, the protein level of acyltransferase, which localizes to peroxisomes, was saturated already at low cluster copy numbers. At higher copy numbers, intracellular levels of isopenicillin N increased, suggesting that the acyltransferase reaction presents a limiting step at a high gene dose. Since the number and appearance of the peroxisomes did not change significantly with the gene cluster copy number, we conclude that the acyltransferase activity is limiting for penicillin biosynthesis at high biosynthetic gene cluster copy numbers. These results suggest that at a high penicillin production level, productivity is limited by the peroxisomal acyltransferase import activity and\/or the availability of coenzyme A (CoA)-activated side chains.\n          <\/jats:p>","DOI":"10.1128\/aem.01702-10","type":"journal-article","created":{"date-parts":[[2010,9,18]],"date-time":"2010-09-18T01:12:08Z","timestamp":1284772328000},"page":"7109-7115","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Nonlinear Biosynthetic Gene Cluster Dose Effect on Penicillin Production by\n            <i>Penicillium chrysogenum<\/i>"],"prefix":"10.1128","volume":"76","author":[{"given":"Jeroen G.","family":"Nijland","sequence":"first","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, Centre for Synthetic Biology, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorg","family":"Ebbendorf","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, Centre for Synthetic Biology, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Woszczynska","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, Centre for Synthetic Biology, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Re\u0301mon","family":"Boer","sequence":"additional","affiliation":[{"name":"DSM Anti-Infectives, A. Fleminglaan 1, 2611 XT Delft, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel A. L.","family":"Bovenberg","sequence":"additional","affiliation":[{"name":"DSM Anti-Infectives, A. Fleminglaan 1, 2611 XT Delft, Netherlands"},{"name":"Synthetic Biology, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold J. M.","family":"Driessen","sequence":"additional","affiliation":[{"name":"Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, Centre for Synthetic Biology, and Kluyver Centre for Genomics of Industrial Fermentation, University of Groningen, Kerklaan 30, 9751 NN Haren, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-003-1274-y"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.13.6200"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-4-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2005.09.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-75"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2007.00232.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10142-009-0110-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2004.10.010"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081257"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02327-09"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(92)90118-E"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb07971.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jim.2900411"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(98)01229-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2008.02.008"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00334395"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2009.02.008"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0290(20000220)72:4<379::AID-BIT1000>3.0.CO;2-5"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1498"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.01702-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AEM.01702-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T17:17:45Z","timestamp":1645636665000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AEM.01702-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11]]},"references-count":19,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2010,11]]}},"alternative-id":["10.1128\/AEM.01702-10"],"URL":"https:\/\/doi.org\/10.1128\/aem.01702-10","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11]]},"assertion":[{"value":"2010-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}