{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:36:48Z","timestamp":1793165808087,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA0910600"],"award-info":[{"award-number":["2021YFA0910600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32570089"],"award-info":[{"award-number":["32570089"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["enviromicro-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Microbial Biotechnology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The filamentous fungus\n                    <jats:italic>Penicillium rubens<\/jats:italic>\n                    is well known as an industrial host for producing penicillin and also used as a promising chassis for secondary metabolite biosynthesis. Chromosomal position effect significantly influences the functional implementation of exogenous genetic modules, but it remains underexplored in filamentous fungi such as\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. rubens<\/jats:italic>\n                    <\/jats:styled-content>\n                    . In this study, a\n                    <jats:italic>PiggyBac<\/jats:italic>\n                    (\n                    <jats:italic>PB<\/jats:italic>\n                    ) transposon\u2010mediated mutagenesis library was constructed in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. rubens<\/jats:italic>\n                    <\/jats:styled-content>\n                    . High\u2010throughput sequencing confirmed a broadly distributed with moderate local hopping of\n                    <jats:italic>PB<\/jats:italic>\n                    insertions across this fungal genome. To characterize the genome position effect, two genomic loci libraries including low\u2010expression (P4) and high\u2010expression (P7) positions were obtained respectively by flow cytometry. Heterologous biosynthesis of the plant\u2010derived anthraquinone physcion in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. rubens<\/jats:italic>\n                    <\/jats:styled-content>\n                    , via targeted integration of its biosynthetic gene cluster (BGC) into the P7 genomic loci, substantially boosted the titre to a level significantly higher than that achieved via integration at the P4 loci, demonstrating a direct correlation between the integration locus and the secondary metabolite output. To our knowledge, this is the first systematic elucidation of chromosomal position effect on heterologous biosynthesis of secondary metabolites in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. rubens<\/jats:italic>\n                    <\/jats:styled-content>\n                    and it also provides an insight for rational selection of integration sites in filamentous fungi.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.70449","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:00:24Z","timestamp":1791525624000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Position Effect Variegation of\n                    <i>Penicillium rubens<\/i>\n                    Genome and Application in Heterologous Production of the Plant\u2010Derived Anthraquinone Physcion"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5443-4863","authenticated-orcid":false,"given":"Meng","family":"Wu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"},{"name":"University of Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1888-5395","authenticated-orcid":false,"given":"Yushi","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"},{"name":"University of Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3307-0897","authenticated-orcid":false,"given":"Linqin","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"},{"name":"University of Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-1683","authenticated-orcid":false,"given":"Yongpeng","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5846-4470","authenticated-orcid":false,"given":"Yuanyuan","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-2985","authenticated-orcid":false,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology Chinese Academy of Sciences  Beijing People's Republic of China"},{"name":"University of Chinese Academy of Sciences  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-016-0619-z"},{"issue":"5","key":"e_1_2_12_3_1","first-page":"494","article-title":"High\u2010Frequency Transformation of Penicillium chrysogenum","volume":"5","author":"Cantoral J. M.","year":"1987","journal-title":"Bio\/Technology"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00324-09"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2019.103279"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01261-x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14450"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.07.013"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25163657"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2008.09.004"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00120216"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90016-8"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2006.03.001"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.2.247-255.2003"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/yea.1705"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016382107"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06944-1"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020156"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)02104-1"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086887"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.113.152744"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2583.1999.00139.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(90)90304-O"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02688-10"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00290129"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0799-1_16"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2013.10.006"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1358"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2021.09.001"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0351-3"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181369"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-018-0936-5"},{"issue":"5","key":"e_1_2_12_33_1","first-page":"649","article-title":"High\u2010Efficiency Thermal Asymmetric Interlaced PCR for Amplification of Unknown Flanking Sequences","volume":"43","author":"Liu Y. G.","year":"2007","journal-title":"Biotechnology Techniques"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10709-006-7165-2"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.1933"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-019-1253-3"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3np70034h"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.04.008"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00082"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2022.10.007"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1945"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms11051132"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.6.2.494-501.1986"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1498"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507683103"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-022-2175-0"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100448"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2012-0048"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof12020136"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-023-12373-y"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008322108"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg341"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2015.12.007"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.035576"}],"container-title":["Microbial Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70449","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1751-7915.70449","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.70449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:19:34Z","timestamp":1793164774000},"score":1,"resource":{"primary":{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/10.1111\/1751-7915.70449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":54,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/1751-7915.70449"],"URL":"https:\/\/doi.org\/10.1111\/1751-7915.70449","archive":["Portico"],"relation":{},"ISSN":["1751-7915","1751-7915"],"issn-type":[{"value":"1751-7915","type":"print"},{"value":"1751-7915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70449"}}