Metabolic Blockade-Based Genome Mining of Sea Anemone-Associated Streptomyces sp. S1502 Identifies Atypical Angucyclines WS-5995 A-E: Isolation, Identification, Biosynthetic Investigation, and Bioactivities

文献类型： 外文期刊

第一作者： Wang, Yuyang

作者： Wang, Yuyang;Zhou, Le;Ju, Jianhua;Ma, Junying;Wang, Yuyang;Ju, Jianhua;Ma, Junying;Pan, Xiaoting;Qi, Nanshan;Sun, Mingfei;Liao, Zhangjun;Zhang, Hua

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关键词： metabolic blockade-based genome mining; Streptomyces sp. S1502; WS-5995; biosynthesis; anticoccidial activity

期刊名称：MARINE DRUGS （ 影响因子：5.4； 五年影响因子：5.5 ）

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年卷期： 2024 年 22 卷 5 期

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收录情况： SCI

摘要： Marine symbiotic and epiphyte microorganisms are sources of bioactive or structurally novel natural products. Metabolic blockade-based genome mining has been proven to be an effective strategy to accelerate the discovery of natural products from both terrestrial and marine microorganisms. Here, the metabolic blockade-based genome mining strategy was applied to the discovery of other metabolites in a sea anemone-associated Streptomyces sp. S1502. We constructed a mutant Streptomyces sp. S1502/Delta stp1 that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster (wsm) of the angucyclines was identified through gene knock-out and heterologous expression studies. The biosynthetic pathways of WS-5995 A-E were proposed, the roles of some tailoring and regulatory genes were investigated, and the biological activities of WS-5995 A-E were evaluated. WS-5995 A has significant anti-Eimeria tenell activity with an IC50 value of 2.21 mu M. The production of antibacterial streptopyrroles and anticoccidial WS-5995 A-E may play a protective role in the mutual relationship between Streptomyces sp. S1502 and its host.

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