Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain
Abstract Four new PKS‐NRPS‐derived macrolide lactams with three unique ring fusion types were discovered from the Arctic sponge associated actinomycete Streptomyces somaliensis 1107 using a genome mining strategy. Their structures were elucidated by a combination of MS, NMR spectroscopic analysis, a...
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Online Access: | http://dx.doi.org/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202218085 |
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crwiley:10.1002/ange.202218085 2024-06-02T08:01:27+00:00 Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain Yang, Fan Sang, Moli Lu, Jing‐Rong Zhao, Hui‐Min Zou, Yike Wu, Wei Yu, Yong Liu, Ya‐Wei Ma, Wencheng Zhang, Yun Zhang, Wei Lin, Hou‐Wen Key Research and Development Program of Hunan Province of China 2023 http://dx.doi.org/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202218085 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Angewandte Chemie volume 135, issue 18 ISSN 0044-8249 1521-3757 journal-article 2023 crwiley https://doi.org/10.1002/ange.202218085 2024-05-03T11:24:41Z Abstract Four new PKS‐NRPS‐derived macrolide lactams with three unique ring fusion types were discovered from the Arctic sponge associated actinomycete Streptomyces somaliensis 1107 using a genome mining strategy. Their structures were elucidated by a combination of MS, NMR spectroscopic analysis, and single‐crystal X‐ray diffraction. Biosynthetically, a novel gene cluster sml consisting of three polyketide synthases and one hybrid polyketide synthase‐nonribosomal peptide synthetase together with cytochrome P450s and flavin‐containing monooxygenases and oxidoreductases was demonstrated to assemble the unique skeleton. Pharmacological studies revealed that compound 1 displayed a potent anti‐inflammatory effect without cytotoxicity. It inhibited IL‐6 and TNF‐α release in the serum of LPS‐stimulated RAW264.7 macrophage cells with IC 50 values of 5.76 and 0.18 μM, respectively, and modulated the MAPK pathway. Moreover, compound 1 alleviated LPS‐induced systemic inflammation in our transgenic fluorescent zebrafish model. Article in Journal/Newspaper Arctic Wiley Online Library Arctic Angewandte Chemie 135 18 |
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Wiley Online Library |
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crwiley |
language |
English |
description |
Abstract Four new PKS‐NRPS‐derived macrolide lactams with three unique ring fusion types were discovered from the Arctic sponge associated actinomycete Streptomyces somaliensis 1107 using a genome mining strategy. Their structures were elucidated by a combination of MS, NMR spectroscopic analysis, and single‐crystal X‐ray diffraction. Biosynthetically, a novel gene cluster sml consisting of three polyketide synthases and one hybrid polyketide synthase‐nonribosomal peptide synthetase together with cytochrome P450s and flavin‐containing monooxygenases and oxidoreductases was demonstrated to assemble the unique skeleton. Pharmacological studies revealed that compound 1 displayed a potent anti‐inflammatory effect without cytotoxicity. It inhibited IL‐6 and TNF‐α release in the serum of LPS‐stimulated RAW264.7 macrophage cells with IC 50 values of 5.76 and 0.18 μM, respectively, and modulated the MAPK pathway. Moreover, compound 1 alleviated LPS‐induced systemic inflammation in our transgenic fluorescent zebrafish model. |
author2 |
Key Research and Development Program of Hunan Province of China |
format |
Article in Journal/Newspaper |
author |
Yang, Fan Sang, Moli Lu, Jing‐Rong Zhao, Hui‐Min Zou, Yike Wu, Wei Yu, Yong Liu, Ya‐Wei Ma, Wencheng Zhang, Yun Zhang, Wei Lin, Hou‐Wen |
spellingShingle |
Yang, Fan Sang, Moli Lu, Jing‐Rong Zhao, Hui‐Min Zou, Yike Wu, Wei Yu, Yong Liu, Ya‐Wei Ma, Wencheng Zhang, Yun Zhang, Wei Lin, Hou‐Wen Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
author_facet |
Yang, Fan Sang, Moli Lu, Jing‐Rong Zhao, Hui‐Min Zou, Yike Wu, Wei Yu, Yong Liu, Ya‐Wei Ma, Wencheng Zhang, Yun Zhang, Wei Lin, Hou‐Wen |
author_sort |
Yang, Fan |
title |
Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
title_short |
Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
title_full |
Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
title_fullStr |
Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
title_full_unstemmed |
Somalactams A–D: Anti‐inflammatory Macrolide Lactams with Unique Ring Systems from an Arctic Actinomycete Strain |
title_sort |
somalactams a–d: anti‐inflammatory macrolide lactams with unique ring systems from an arctic actinomycete strain |
publisher |
Wiley |
publishDate |
2023 |
url |
http://dx.doi.org/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202218085 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ange.202218085 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Angewandte Chemie volume 135, issue 18 ISSN 0044-8249 1521-3757 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/ange.202218085 |
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Angewandte Chemie |
container_volume |
135 |
container_issue |
18 |
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1800745828238753792 |