{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:49:15Z","timestamp":1781322555593,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2100600"],"award-info":[{"award-number":["2021YFC2100600"]}],"id":[{"id":"10.13039\/501100012166","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":[[2022,5]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Heterologous expression of the biosynthetic gene cluster (BGC) is important for studying the microbial natural products (NPs), especially for those kept in silent or poorly expressed in their original strains. Here, we cloned the spinosad BGC through the Cas9\u2010Assisted Targeting of Chromosome segments and amplified it to five copies through a ZouA\u2010dependent DNA amplification system in\n                    <jats:italic>Streptomyces coelicolor<\/jats:italic>\n                    M1146. The resulting strain produced 1253.9\u00a0\u00b1\u00a078.2\u00a0\u03bcg\u00a0l\n                    <jats:sup>\u22121<\/jats:sup>\n                    of spinosad, which was about 224\u2010fold compared with that of the parent strain carrying only one copy of the spinosad BGC. Moreover, we further increased spinosad to 1958.9\u00a0\u00b1\u00a073.5\u00a0\u03bcg\u00a0l\n                    <jats:sup>\u22121<\/jats:sup>\n                    by the dynamic regulation of intracellular triacylglycerol degradation. Our study indicates that tandem amplification of the targeted gene cluster is particularly suitable to enhance the heterologous production of valuable NPs with efficiency and simplicity.\n                  <\/jats:p>","DOI":"10.1111\/1751-7915.13965","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T01:45:37Z","timestamp":1637286337000},"page":"1550-1560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multiplying the heterologous production of spinosad through tandem amplification of its biosynthetic gene cluster in\n                    <i>Streptomyces coelicolor<\/i>"],"prefix":"10.1111","volume":"15","author":[{"given":"Hong","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 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 Mycology Institute of Microbiology Chinese Academy of Sciences  Beijing 100101 China"},{"name":"University of Chinese Academy of Sciences  Beijing 100049 China"},{"name":"The Innovative Academy of Seed Design Chinese Academy of Sciences  Beijing 100864 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4NP00144C"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084151"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.21493"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2183"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9373"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-7915.2010.00219.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-013-1348-5"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8NP00091C"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2013.10.008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9101"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.055"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0069319"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-015-1723-5"},{"key":"e_1_2_8_16_1","volume-title":"Practical Streptomyces Genetics","author":"Kieser T.","year":"2000"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/sb3001003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.491"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7384"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-021-1998-8"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-61779-564-0_5"},{"key":"e_1_2_8_22_1","first-page":"608","article-title":"The future of 520 natural products as a source of new antibiotics","volume":"8","author":"Luzhetskyy A.","year":"2007","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.19.5632-5638.2001"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt833"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90831-1"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-40-1-34"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1507606112"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1108124108"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/np200906s"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-10"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiosc.2021.01.002"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3np70034h"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-12-65"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-013-1352-9"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.8b00402"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.358"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00330"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2016.12.006"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120147"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(01)00029-1"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0187-0"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.054"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0335-4"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319584111"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603251103"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6968.12183"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-014-5943-9"}],"container-title":["Microbial Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.13965","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1751-7915.13965","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1751-7915.13965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T14:10:58Z","timestamp":1762265458000},"score":1,"resource":{"primary":{"URL":"https:\/\/sfamjournals.onlinelibrary.wiley.com\/doi\/10.1111\/1751-7915.13965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1111\/1751-7915.13965"],"URL":"https:\/\/doi.org\/10.1111\/1751-7915.13965","archive":["Portico"],"relation":{},"ISSN":["1751-7915","1751-7915"],"issn-type":[{"value":"1751-7915","type":"print"},{"value":"1751-7915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,18]]},"assertion":[{"value":"2021-08-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}