{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:37:09Z","timestamp":1789760229042,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"50","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2020,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The colinearity of canonical modular polyketide synthases, which creates a direct link between multienzyme structure and the chemical structure of the biosynthetic end\u2010product, has become a cornerstone of knowledge\u2010based genome mining. Herein, we report genetic and enzymatic evidence for the remarkable role of an enoylreductase in the polyketide synthase for azalomycin F biosynthesis. This internal enoylreductase domain, previously identified as acting only in the second of two chain extension cycles on an initial iterative module, is shown to also catalyze enoylreduction <jats:italic>in trans<\/jats:italic> within the next module. The mechanism for this rare deviation from colinearity appears to involve direct cross\u2010modular interaction of the reductase with the longer acyl chain, rather than back transfer of the substrate into the iterative module, suggesting an additional and surprising plasticity in natural PKS assembly\u2010line catalysis.<\/jats:p>","DOI":"10.1002\/anie.202011357","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T10:28:36Z","timestamp":1598869716000},"page":"22738-22742","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cross\u2010Module Enoylreduction in the Azalomycin\u2005F Polyketide Synthase"],"prefix":"10.1002","volume":"59","author":[{"given":"Guifa","family":"Zhai","sequence":"first","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Molecular Sciences Wuhan University  No. 299 Bayi Road Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"},{"name":"Current address: Singapore Institute of Food and Biotechnology Innovation Agency for Science, Technology, and Research (A*STAR)  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqun","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangming","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zisong","family":"Cong","sequence":"additional","affiliation":[{"name":"College of Chemistry and Molecular Sciences Wuhan University  No. 299 Bayi Road Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanrong","family":"Shi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Leadlay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Cambridge  No. 80 Tennis Court Road Cambridge CB2 1GA UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Song","sequence":"additional","affiliation":[{"name":"College of Chemistry and Molecular Sciences Wuhan University  No. 299 Bayi Road Wuhan 430072 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Hong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road 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 Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5720-9620","authenticated-orcid":false,"given":"Yuhui","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Wuhan University) Ministry of Education, and School of Pharmaceutical Sciences Wuhan University  No. 185 East Lake Road Wuhan 430071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2016.05.009"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/348176a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2024119"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0537286100"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1379"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113029109"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(00)00076-4"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111738200"},{"key":"e_1_2_6_9_1","unstructured":"\u00a0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200400333"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201308176"},{"key":"e_1_2_6_11_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201308176"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201911315"},{"key":"e_1_2_6_12_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201911315"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/B310648A"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.12.206"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0215958"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35000624"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(01)00024-2"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja030503f"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201703588"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201703588"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09748"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.9.3468-3476.2004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201701220"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201701220"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058092"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi020006w"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201308136"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201308136"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.15.7119"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201500017"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.7b00982"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.964"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/b315020h"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202011357","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202011357","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202011357","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T02:19:29Z","timestamp":1692757169000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202011357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":35,"journal-issue":{"issue":"50","published-print":{"date-parts":[[2020,12,7]]}},"alternative-id":["10.1002\/anie.202011357"],"URL":"https:\/\/doi.org\/10.1002\/anie.202011357","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,8]]},"assertion":[{"value":"2020-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}