{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:09:41Z","timestamp":1790633381950,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T00:00:00Z","timestamp":1713657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2018YFA0901900"],"award-info":[{"award-number":["2018YFA0901900"]}]},{"name":"the National Key Research and Development Program of China","award":["TSBICIP-CXRC-076"],"award-info":[{"award-number":["TSBICIP-CXRC-076"]}]},{"name":"the National Key Research and Development Program of China","award":["22HHSWSS00001"],"award-info":[{"award-number":["22HHSWSS00001"]}]},{"name":"the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project","award":["2018YFA0901900"],"award-info":[{"award-number":["2018YFA0901900"]}]},{"name":"the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project","award":["TSBICIP-CXRC-076"],"award-info":[{"award-number":["TSBICIP-CXRC-076"]}]},{"name":"the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project","award":["22HHSWSS00001"],"award-info":[{"award-number":["22HHSWSS00001"]}]},{"name":"the \u201cMajor Project\u201d of Haihe Laboratory of Synthetic Biology","award":["2018YFA0901900"],"award-info":[{"award-number":["2018YFA0901900"]}]},{"name":"the \u201cMajor Project\u201d of Haihe Laboratory of Synthetic Biology","award":["TSBICIP-CXRC-076"],"award-info":[{"award-number":["TSBICIP-CXRC-076"]}]},{"name":"the \u201cMajor Project\u201d of Haihe Laboratory of Synthetic Biology","award":["22HHSWSS00001"],"award-info":[{"award-number":["22HHSWSS00001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23\/5\/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10\u20130.83 \u03bcg\/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 \u03bcg\/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 \u00b5M.<\/jats:p>","DOI":"10.3390\/md22040189","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T03:57:07Z","timestamp":1713758227000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-Derived Streptomyces sp. DSS69, by Heterologous Expression"],"prefix":"10.3390","volume":"22","author":[{"given":"Lu","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Hong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanzhao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yemin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Haihe Laboratory of Synthetic Biology, Tianjin 300308, China"},{"name":"Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-7591","authenticated-orcid":false,"given":"Meifeng","family":"Tao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China"},{"name":"Haihe Laboratory of Synthetic Biology, Tianjin 300308, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1039\/D0NP00050G","article-title":"Natural polyenic macrolactams and polycyclic derivatives generated by transannular pericyclic reactions: Optimized biogenesis challenging chemical synthesis","volume":"38","author":"Alvarez","year":"2021","journal-title":"Nat. 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