{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:12:15Z","timestamp":1787242335332,"version":"build-2736575974"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U24A20346"],"award-info":[{"award-number":["U24A20346"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Science and Technology Plan Projects in Nansha District","award":["2023ZD010"],"award-info":[{"award-number":["2023ZD010"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFA0914200"],"award-info":[{"award-number":["2023YFA0914200"]}]},{"name":"National Key Research and Development Program of China","award":["2024YFC2816000"],"award-info":[{"award-number":["2024YFC2816000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Nenestatins (NENs) belong to benzo[b]fluorene-containing atypical angucyclines, a structurally diverse class of microbial natural products. Bioinformatic analysis of the NEN biosynthetic gene cluster (nes BGC) from the deep-sea sediment-derived Micromonospora echinospora SCSIO 04089 implicated Nes5 as an \u03b1\/\u03b2 hydrolase. The targeted inactivation of the nes5 gene led to the accumulation of five new analogs, NENs E\u2013I (1\u20135), together with the known monomer homo-dehydrorabelomycin E (6). Their structures were elucidated by comprehensive spectroscopic analysis and electronic circular dichroism calculations. Notably, both NEN A and NEN B were absent in the \u0394nes5 mutant, indicating that Nes5 is essential for their biosynthesis; however, the exact function of Nes5 requires further exploration.<\/jats:p>","DOI":"10.3390\/md24030103","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:58:45Z","timestamp":1773046725000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted Inactivation of an \u03b1\/\u03b2 Hydrolase Gene Enables Discovery of Heterodimeric Nenestatins"],"prefix":"10.3390","volume":"24","author":[{"given":"Wenzheng","family":"Wei","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Marine Drugs, University Engineering Research Center of High-Efficient Utilization of Marine Traditional Chinese Medicine Resources, Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8737-8898","authenticated-orcid":false,"given":"Yiguang","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2677-3752","authenticated-orcid":false,"given":"Wenjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-2730","authenticated-orcid":false,"given":"Qingbo","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-3138","authenticated-orcid":false,"given":"Changsheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China"},{"name":"University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1039\/C1NP00068C","article-title":"Angucyclines: Biosynthesis, mode-of-action, new natural products, and synthesis","volume":"29","author":"Kharel","year":"2012","journal-title":"Nat. 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