{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:01:53Z","timestamp":1792609313354,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31670090"],"award-info":[{"award-number":["31670090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:label\/><jats:p>Spinosad is a potent insecticide that exhibits an excellent environmental and mammalian profile. However, spinosad production in the original producer, <jats:italic>Saccharopolyspora spinosa<\/jats:italic>, is insufficient for the huge global demand. Great efforts have been exerted to improve the production of spinosad. Strategies for spinosad overproduction in actinomycetes are reviewed in this article, including metabolic engineering of the precursor and spinosyn biosynthetic pathway, introduction of regulatory genes, genome\u2010scale metabolic model\u2010guided engineering, mutagenesis, genome shuffling, fermentation process optimization, omics analysis, and the heterologous biosynthesis of spinosad in other actinomycetes. Furthermore, highly productive industrial strains should be used as heterologous hosts for enhancing spinosad biosynthesis in the future. To accelerate the engineering process, the CRISPR\/Cas9 system should be established in <jats:italic>Sa. spinosa<\/jats:italic> for large\u2010scale genome editing. Notably, the regulatory mechanism of spinosad biosynthesis remains unclear. Thus, the combining multi\u2010omics analysis with high\u2010throughput screening of chemical elicitors would be a promising approach in characterizing the regulatory and signal transduction mechanisms and improving spinosad production in <jats:italic>Sa. Spinosa<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/biot.201700769","type":"journal-article","created":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T09:27:29Z","timestamp":1528882049000},"source":"Crossref","is-referenced-by-count":53,"title":["Strategies for Enhancing the Yield of the Potent Insecticide Spinosad in Actinomycetes"],"prefix":"10.1002","volume":"14","author":[{"given":"Hui","family":"Tao","sequence":"first","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education and Wuhan University School of Pharmaceutical Sciences Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education and Wuhan University School of Pharmaceutical Sciences Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education and Wuhan University School of Pharmaceutical Sciences Wuhan 430071 P. R. China"},{"name":"Hubei Engineering Laboratory for Synthetic Microbiology Wuhan Institute of Biotechnology Wuhan 430075 P. R. China"},{"name":"State Key Laboratory of Microbial Metabolism, and School of Life Sciences and Biotechnology Shanghai Jiao Tong University Shanghai 200240 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiangang","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education and Wuhan University School of Pharmaceutical Sciences Wuhan 430071 P. R. China"},{"name":"Hubei Engineering Laboratory for Synthetic Microbiology Wuhan Institute of Biotechnology Wuhan 430075 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,5]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2009.04.009"},{"key":"e_1_2_8_2_1","first-page":"12","volume":"60","author":"Salgado V. L.","year":"1998","journal-title":"Pestic Biochem Phys"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.424"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jspr.2011.01.004"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2011.11.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2007.09.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2011.11.026"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)93474-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bk-1992-0504.ch020"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010289901631"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(01)00029-1"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja042702k"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0649670"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja076580i"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja0771383"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-008-0431-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808441200"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja910223x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09981"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201407806"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1768"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700484"},{"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\/sj.jim.7000180"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-010-0481-8"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.14348\/molcells.2014.0168","volume":"37","author":"Jha A. K.","year":"2014","journal-title":"Mol. Cells"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2013.10.004"},{"key":"e_1_2_8_28_1","first-page":"27","volume":"10","author":"Jha A. K.","year":"2013","journal-title":"J. Biomolecule Reconstruction"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2015.104"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2011.02405.x"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2013.01.007"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00344-11"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-13-41"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.2006.AS0366"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-008-8281-5"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-008-8500-0"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13213-014-0917-9"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01583684"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1004-9541(06)60111-0"},{"key":"e_1_2_8_40_1","first-page":"e16765","volume":"9","author":"Yang G.","year":"2016","journal-title":"Jundishapur J. Microb"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-012-4276-0"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.12264"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-5956-9-40"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2859-13-27"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-015-6883-8"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.130169"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10482-017-0835-5"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-010-0730-9"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00618-16"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000477543"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.6b00330"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2016.12.006"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2004.08.019"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700465"},{"key":"e_1_2_8_55_1","first-page":"1700465","volume":"12","author":"Xinran W.","year":"2017","journal-title":"Biotechnol. J"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-140-1-139"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(94)90831-1"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-015-6871-z"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201600145"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/sb500351f"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.5b00038"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-015-6931-4"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-013-1387-y"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2014.12.003"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.06.013"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400019111"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi5003629"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbiot.201700769","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.201700769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:03:28Z","timestamp":1759950208000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.201700769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,5]]},"references-count":67,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/biot.201700769"],"URL":"https:\/\/doi.org\/10.1002\/biot.201700769","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,5]]},"article-number":"1700769"}}