CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Haizhu District, Guangzhou 510301, China.
College of Oceanology, University of Chinese Academy of Sciences, Qingdao 266400, China.
Mar Drugs. 2024 Apr 25;22(5):195. doi: 10.3390/md22050195.
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 sp. S1502. We constructed a mutant sp. S1502/Δ that switched to producing the atypical angucyclines WS-5995 A-E, among which WS-5995 E is a new compound. A biosynthetic gene cluster () 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- activity with an IC 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 sp. S1502 and its host.
海洋共生和附生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发现陆地和海洋微生物中天然产物的有效策略。在这里，我们将基于代谢阻断的基因组挖掘策略应用于发现与海葵相关的 sp. S1502 中的其他代谢产物。我们构建了一个突变体 sp. S1502/Δ，它转而产生非典型的蒽环类化合物 WS-5995 A-E，其中 WS-5995 E 是一种新化合物。通过基因敲除和异源表达研究，鉴定了蒽环类化合物的生物合成基因簇 ()。提出了 WS-5995 A-E 的生物合成途径，研究了一些修饰和调节基因的作用，并评估了 WS-5995 A-E 的生物活性。WS-5995 A 具有显著的抗活性，IC 值为 2.21 μM。抗菌链霉菌吡咯和抗球虫 WS-5995 A-E 的产生可能在 sp. S1502 与其宿主之间的相互关系中发挥保护作用。
