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

Autor: Yuyang Wang, Le Zhou, Xiaoting Pan, Zhangjun Liao, Nanshan Qi, Mingfei Sun, Hua Zhang, Jianhua Ju, Junying Ma
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Marine Drugs, Vol 22, Iss 5, p 195 (2024)
Druh dokumentu: article
ISSN: 1660-3397
DOI: 10.3390/md22050195
Popis: 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.
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