{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:29:58Z","timestamp":1762522198499,"version":"3.37.3"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"20","license":[{"start":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T00:00:00Z","timestamp":1534550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"the National Major Scientific and Technological Special Project for \u201cSignificant New Drugs Development\u201d","award":["2014ZX09201001-005-001"],"award-info":[{"award-number":["2014ZX09201001-005-001"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31770088 and 31570072"],"award-info":[{"award-number":["31770088 and 31570072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Derivative Bank of Chinese Biological Resources, CAS","award":["ZSYS-016"],"award-info":[{"award-number":["ZSYS-016"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Appl Microbiol Biotechnol"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1007\/s00253-018-9280-2","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T00:28:05Z","timestamp":1534552085000},"page":"8841-8853","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["MilR2, a novel TetR family regulator involved in 5-oxomilbemycin A3\/A4 biosynthesis in Streptomyces hygroscopicus"],"prefix":"10.1007","volume":"102","author":[{"given":"Keke","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanjie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinhua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoxin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,8,18]]},"reference":[{"issue":"1","key":"9280_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0378-1119(92)90627-2","volume":"116","author":"M Bierman","year":"1992","unstructured":"Bierman M, Logan R, O'Brien K, Seno ET, Rao RN, Schoner BE (1992) Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116(1):43\u201349","journal-title":"Gene"},{"issue":"3","key":"9280_CR2","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1128\/AAC.15.3.361","volume":"15","author":"RW Burg","year":"1979","unstructured":"Burg RW, Miller BM, Baker EE, Birnbaum J, Currie SA, Hartman R, Kong YL, Monaghan RL, Olson G, Putter I, Tunac JB, Wallick H, Stapley EO, Oiwa R, Omura S (1979) Avermectins, new family of potent anthelmintic agents: producing organism and fermentation. Antimicrob Agents Chemother 15(3):361\u2013367","journal-title":"Antimicrob Agents Chemother"},{"issue":"3","key":"9280_CR3","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1128\/JB.02312-14","volume":"197","author":"JL Dun","year":"2015","unstructured":"Dun JL, Zhao YW, Zheng GS, Zhu H, Ruan LJ, Wang WF, Ge M, Jiang WH, Lu YH (2015) PapR6, a putative atypical response regulator, functions as a pathway-specific activator of pristinamycin II biosynthesis in Streptomyces pristinaespiralis. J Bacteriol 197(3):441\u2013450","journal-title":"J Bacteriol"},{"issue":"10","key":"9280_CR4","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.1128\/AEM.02262-09","volume":"76","author":"YL He","year":"2010","unstructured":"He YL, Sun YH, Liu TG, Zhou XF, Bai LQ, Deng ZX (2010) Cloning of separate meilingmycin biosynthesis gene clusters by use of acyltransferase-ketoreductase didomain PCR amplification. Appl Environ Microbiol 76(10):3283\u20133292","journal-title":"Appl Environ Microbiol"},{"issue":"1","key":"9280_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1271\/bbb.120735","volume":"77","author":"H Ichinose","year":"2013","unstructured":"Ichinose H, Fujimoto Z, Kaneko S (2013) Characterization of an \u03b1-L-rhamnosidase from Streptomyces avermitilis. Biosci Biotechnol Biochem 77(1):213\u2013216","journal-title":"Biosci Biotechnol Biochem"},{"issue":"1","key":"9280_CR6","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12934-017-0626-8","volume":"16","author":"MS Kim","year":"2017","unstructured":"Kim MS, Cho WJ, Song MC, Park SW, Kim K, Kim E, Lee N, Nam SJ, Oh KH, Yoon YJ (2017) Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis. Microb Cell Factories 16(1):9","journal-title":"Microb Cell Factories"},{"issue":"4","key":"9280_CR7","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method. Methods 25(4):402\u2013408","journal-title":"Methods"},{"key":"9280_CR8","unstructured":"Mishima H, Kurabayashi M, Tamura C, Sato S, Kuwano H, Saito A, Aoki A (1974) Structures of milbemycins \u03b11, \u03b12, \u03b13, \u03b14, \u03b15, \u03b16, \u03b17, \u03b18, \u03b19, \u03b110 and \u03b21. Abstract Papers 18th Symp. Chem Natural Products, symposium papers 18(0):309\u2013316"},{"issue":"10","key":"9280_CR9","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/S0040-4039(00)71964-2","volume":"16","author":"H Mishima","year":"1975","unstructured":"Mishima H, Kurabayashi M, Tamura C, Sato S, Kuwano H, Saito A, Aoki A (1975) Structures of milbemycin \u03b21, \u03b22, and \u03b23. Tetrahedron Lett 16(10):711\u2013714","journal-title":"Tetrahedron Lett"},{"issue":"15","key":"9280_CR10","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1128\/AEM.00434-11","volume":"77","author":"M Myronovskyi","year":"2011","unstructured":"Myronovskyi M, Welle E, Fedorenko V, Luzhetskyy A (2011) Glucuronidase as a sensitive and versatile reporter in actinomycetes. Appl Environ Microbiol 77(15):5370\u20135383","journal-title":"Appl Environ Microbiol"},{"issue":"2","key":"9280_CR11","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1128\/MMBR.69.2.326-356.2005","volume":"69","author":"JL Ramos","year":"2005","unstructured":"Ramos JL, Martinez-Bueno M, Molina-Henares AJ, Teran W, Watanabe K, Zhang X, Gallegos MT, Brennan R, Tobes R (2005) The TetR family of transcriptional repressors. Microbiol Mol Biol Rev 69(2):326\u2013356","journal-title":"Microbiol Mol Biol Rev"},{"issue":"5","key":"9280_CR12","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1093\/nar\/20.5.961","volume":"20","author":"WR Strohl","year":"1992","unstructured":"Strohl WR (1992) Compilation and analysis of DNA sequences associated with apparent streptomycete promoters. Nucleic Acids Res 20(5):961\u2013974","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"9280_CR13","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1111\/j.1365-2958.2007.06092.x","volume":"67","author":"Y Tiffert","year":"2008","unstructured":"Tiffert Y, Supra P, Wurm R, Wohlleben W, Wagner R, Reuther J (2008) The Streptomyces coelicolor GlnR regulon: identification of new GlnR targets and evidence for a central role of GlnR in nitrogen metabolism in actinomycetes. Mol Microbiol 67(4):861\u2013880","journal-title":"Mol Microbiol"},{"issue":"19","key":"9280_CR14","doi-asserted-by":"publisher","first-page":"5237","DOI":"10.1128\/JB.00989-12","volume":"194","author":"Y Wang","year":"2012","unstructured":"Wang Y, Cen XF, Zhao GP, Wang J (2012) Characterization of a new GlnR binding box in the promoter of amtB in Streptomyces coelicolor inferred a PhoP\/GlnR competitive binding mechanism for transcriptional regulation of amtB. J Bacteriol 194(19):5237\u20135244","journal-title":"J Bacteriol"},{"issue":"6","key":"9280_CR15","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/ja.2009.33","volume":"62","author":"XJ Wang","year":"2009","unstructured":"Wang XJ, Guo SL, Guo WQ, Xi D, Xiang WS (2009) Role of nsdA in negative regulation of antibiotic production and morphological differentiation in Streptomyces bingchengensis. J Antibiot (Tokyo) 62(6):309\u2013313","journal-title":"J Antibiot (Tokyo)"},{"issue":"1","key":"9280_CR16","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1111\/mmi.12080","volume":"87","author":"R Wang","year":"2013","unstructured":"Wang R, Mast Y, Wang J, Zhang WW, Zhao GP, Wohlleben W, Lu YH, Jiang WH (2013) Identification of two-component system AfsQ1\/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor. Mol Microbiol 87(1):30\u201348","journal-title":"Mol Microbiol"},{"issue":"17","key":"9280_CR17","doi-asserted-by":"publisher","first-page":"4526","DOI":"10.1128\/JB.00596-10","volume":"192","author":"XJ Wang","year":"2010","unstructured":"Wang XJ, Yan YJ, Zhang B, An J, Wang JJ, Tian J, Jiang L, Chen YH, Huang SX, Yin M, Zhang J, Gao AL, Liu CX, Zhu ZX, Xiang WS (2010) Genome sequence of the milbemycin-producing bacterium Streptomyces bingchenggensis. J Bacteriol 192(17):4526\u20134527","journal-title":"J Bacteriol"},{"issue":"11","key":"9280_CR18","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1139\/gen-2013-0098","volume":"56","author":"XJ Wang","year":"2013","unstructured":"Wang XJ, Zhang B, Yan YJ, An J, Zhang J, Liu CX, Xiang WS (2013) Characterization and analysis of an industrial strain of Streptomyces bingchenggensis by genome sequencing and gene microarray. Genome 56(11):677\u2013689","journal-title":"Genome"},{"issue":"23","key":"9280_CR19","doi-asserted-by":"publisher","first-page":"9703","DOI":"10.1007\/s00253-014-5970-6","volume":"98","author":"HY Wang","year":"2014","unstructured":"Wang HY, Zhang J, Zhang YJ, Zhang B, Liu CX, He HR, Wang XJ, Xiang WS (2014) Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3\/A4 as main components from Streptomyces bingchenggensis. Appl Microbiol Biotechnol 98(23):9703\u20139712","journal-title":"Appl Microbiol Biotechnol"},{"issue":"4","key":"9280_CR20","first-page":"417","volume":"4","author":"CJ Wilkinson","year":"2002","unstructured":"Wilkinson CJ, Hughes-Thomas ZA, Martin CJ, Bohm I, Mironenko T, Deacon M, Wheatcroft M, Wirtz G, Staunton J, Leadlay PF (2002) Increasing the efficiency of heterologous promoters in actinomycetes. J Mol Microbiol Biotechnol 4(4):417\u2013426","journal-title":"J Mol Microbiol Biotechnol"},{"issue":"6","key":"9280_CR21","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/ja.2007.47","volume":"60","author":"WS Xiang","year":"2007","unstructured":"Xiang WS, Wang JD, Wang XJ, Zhang J (2007) Two new beta-class milbemycins from streptomyces bingchenggensis: fermentation, isolation, structure elucidation and biological properties. J Antibiot (Tokyo) 60(6):351\u2013356","journal-title":"J Antibiot (Tokyo)"},{"issue":"10","key":"9280_CR22","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/ja.2007.78","volume":"60","author":"WS Xiang","year":"2007","unstructured":"Xiang WS, Wang JD, Wang XJ, Zhang J, Wang Z (2007) Further new milbemycin antibiotics from Streptomyces bingchenggensis. Fermentation, isolation, structural elucidation and biological activities. J Antibiot (Tokyo) 60(10):608\u2013613","journal-title":"J Antibiot (Tokyo)"},{"issue":"23","key":"9280_CR23","doi-asserted-by":"publisher","first-page":"10091","DOI":"10.1007\/s00253-013-5255-5","volume":"97","author":"J Zhang","year":"2013","unstructured":"Zhang J, An J, Wang JJ, Yan YJ, He HR, Wang XJ, Xiang WS (2013) Genetic engineering of Streptomyces bingchenggensis to produce milbemycins A3\/A4 as main components and eliminate the biosynthesis of nanchangmycin. Appl Microbiol Biotechnol 97(23):10091\u201310101","journal-title":"Appl Microbiol Biotechnol"},{"issue":"1","key":"9280_CR24","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12934-016-0552-1","volume":"15","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, He H, Liu H, Wang H, Wang X, Xiang W (2016) Characterization of a pathway-specific activator of milbemycin biosynthesis and improved milbemycin production by its overexpression in Streptomyces bingchenggensis. Microb Cell Factories 15(1):152","journal-title":"Microb Cell Factories"}],"container-title":["Applied Microbiology and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00253-018-9280-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-018-9280-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00253-018-9280-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,17]],"date-time":"2019-08-17T19:24:31Z","timestamp":1566069871000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00253-018-9280-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,18]]},"references-count":24,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["9280"],"URL":"https:\/\/doi.org\/10.1007\/s00253-018-9280-2","relation":{},"ISSN":["0175-7598","1432-0614"],"issn-type":[{"type":"print","value":"0175-7598"},{"type":"electronic","value":"1432-0614"}],"subject":[],"published":{"date-parts":[[2018,8,18]]},"assertion":[{"value":"28 April 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All of the authors confirm that ethical principles have been followed in the research as well as in manuscript preparation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical statement"}}]}}