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By interfering with zinc ion homeostasis in living cells, they show strong antibacterial activity against a variety of bacterial pathogens, as well as potent cytotoxicity against human cancer cells. In the current study, two new dithiolopyrrolones, pyrroloformamide C (3) and pyrroloformamide D (4), were isolated from Streptomyces sp. CB02980, together with the known pyrroloformamides 1 and 2. The biosynthetic gene cluster for pyrroloformamides was identified from Streptomyces sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of pyfE, which encodes a nonribosomal peptide synthetase (NRPS), abolished the production of 1\u20134. Overexpression of pyfN, a type II thioesterase gene, increased the production of 1 and 2. Genome neighborhood network analysis of the characterized and orphan gene clusters of dithiolopyrrolones revealed a unified mechanism for their biosynthesis, involving an iterative-acting NRPS and a set of conserved tailoring enzymes for the bicyclic core formation.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.9b00321","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T12:57:33Z","timestamp":1581512253000},"page":"202-209","source":"Crossref","is-referenced-by-count":11,"title":["The Isolation of Pyrroloformamide Congeners and Characterization\nof Their Biosynthetic Gene Cluster"],"prefix":"10.1021","volume":"83","author":[{"given":"Wenqing","family":"Zhou","sequence":"first","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Liang","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-1368","authenticated-orcid":true,"given":"Xiangjing","family":"Qin","sequence":"additional","affiliation":[{"name":"South China Sea Institute of Oceanology, Chinese Academy of Sciences , , ,","place":["Guangzhou, People\u2019s Republic of China, 510301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danfeng","family":"Cao","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangcheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]},{"name":"Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discover , , ,","place":["Changsha, Hunan, People\u2019s\nRepublic of China, 410011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-8027","authenticated-orcid":true,"given":"Jianhua","family":"Ju","sequence":"additional","affiliation":[{"name":"South China Sea Institute of Oceanology, Chinese Academy of Sciences , , ,","place":["Guangzhou, People\u2019s Republic of China, 510301"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-5982","authenticated-orcid":true,"given":"Ben","family":"Shen","sequence":"additional","affiliation":[{"name":"Scripps Research , , , ,","place":["Jupiter, Florida, United States, 33458"]},{"name":"Scripps Research , , , ,","place":["Jupiter, Florida, United States, 33458"]},{"name":"Scripps Research , , , ,","place":["Jupiter, Florida, United States, 33458"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Duan","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]},{"name":"Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discover , , ,","place":["Changsha, Hunan, People\u2019s\nRepublic of China, 410011"]},{"name":"National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery , , ,","place":["Changsha, Hunan, People\u2019s Republic of China, 410011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3163-1716","authenticated-orcid":true,"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine at Central South University , , ,","place":["Changsha, Hunan, People\u2019s Republic\nof China, 410013"]},{"name":"National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery , , ,","place":["Changsha, Hunan, People\u2019s Republic of China, 410011"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,2,12]]},"reference":[{"key":"2026081719094666200_cit1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2113\/gselements.6.2.75","volume":"6","author":"Mandeville","year":"2010","journal-title":"Elements"},{"key":"2026081719094666200_cit2","doi-asserted-by":"publisher","first-page":"334","DOI":"10.7164\/antibiotics.30.334","volume":"30","author":"Okamura","year":"1977","journal-title":"J. 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