{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T01:33:43Z","timestamp":1769909623789,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"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":["31730002"],"award-info":[{"award-number":["31730002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The efficiency of drug biosynthesis depends on different transcriptional regulatory pathways in <jats:italic>Streptomyces<\/jats:italic>, and the protein degradation system adds another layer of complexity to the regulatory processes. AtrA, a transcriptional regulator in the A\u2010factor regulatory cascade, stimulates the production of daptomycin by binding to the <jats:italic>dptE<\/jats:italic> promoter in <jats:italic>Streptomyces roseosporus<\/jats:italic>. Using pull\u2010down assays, bacterial two\u2010hybrid system and knockout verification, we demonstrated that AtrA is a substrate for ClpP protease. Furthermore, we showed that ClpX is necessary for AtrA recognition and subsequent degradation. Bioinformatics analysis, truncating mutation, and overexpression proved that the AAA motifs of AtrA were essential for initial recognition in the degradation process. Finally, overexpression of mutated <jats:italic>atrA<\/jats:italic> (AAA\u2010QQQ) in <jats:italic>S. roseosporus<\/jats:italic> increased the yield of daptomycin by 225% in shake flask and by 164% in the 15\u2009L bioreactor. Thus, improving the stability of key regulators is an effective method to promote the ability of antibiotic synthesis.<\/jats:p>","DOI":"10.1002\/pro.4617","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T05:28:42Z","timestamp":1678253322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Degradation mechanism of <scp>AtrA<\/scp> mediated by <scp>ClpXP<\/scp> and its application in daptomycin production in <i>Streptomyces roseosporus<\/i>"],"prefix":"10.1002","volume":"32","author":[{"given":"Wei\u2010Feng","family":"Xu","sequence":"first","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Fan","family":"Sun","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Li","family":"Gao","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel H.","family":"Scharf","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Yang","family":"Zhu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing\u2010Ting","family":"Bu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing\u2010Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6013-4068","authenticated-orcid":false,"given":"Yong\u2010Quan","family":"Li","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital and Institute of Pharmaceutical Biotechnology Zhejiang University School of Medicine  Hangzhou China"},{"name":"Institute of Pharmaceutical Biotechnology Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00144-20"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00591-15"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01174"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00302-15"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01364.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-019-01719-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52774"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00060-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.048454-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-14-81"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-013-0918-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/014381-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2020.09.012"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5488.2354"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-019-10062-3"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.872397"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-017-1983-3"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.608273"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.491498"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27757-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.180.20.5448-5453.1998"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.9.1.27"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163885"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1597"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-0924-2"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04817.x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-015-6638-6"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-022-11904-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-018-02127-5"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.4617","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pro.4617","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.4617","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:31:54Z","timestamp":1715171514000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.4617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,22]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/pro.4617"],"URL":"https:\/\/doi.org\/10.1002\/pro.4617","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,22]]},"assertion":[{"value":"2022-11-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4617"}}