PDF(Pubmed)
Abstract：
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/Δstp1 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 μM. 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.
摘要：
海洋共生和附生植物微生物是生物活性或结构新颖的天然产物的来源。基于代谢阻断的基因组挖掘已被证明是加速从陆地和海洋微生物中发现天然产物的有效策略。这里,基于代谢阻断的基因组挖掘策略被应用于在海葵相关链霉菌中发现其他代谢物。S1502.我们构建了一个突变体链霉菌。S1502/Δstp1转换为生产非典型angucyclesWS-5995A-E，其中WS-5995E是一种新化合物。通过基因敲除和异源表达研究鉴定了angucycles的生物合成基因簇（wsm）。提出了WS-5995A-E的生物合成途径，研究了一些剪裁和调节基因的作用，并对WS-5995A-E的生物学活性进行了评价。WS-5995A具有显著的抗艾美球虫活性,IC50值为2.21μM。抗菌链霉素和抗球虫WS-5995A-E的产生可能在链霉菌之间的相互关系中起保护作用。S1502及其主机。
