Discovery of New Angucyclin(on)e Derivatives and Their Genetic Architecture from Streptomyces sp. SYP-A7185 in the Rhizosphere Soil of Panax notoginseng

Strain SYP-A7185 was isolated from the rhizosphere soil of Panax notoginseng (Burk.) F. H. Chen, a medicinal plant in Wenshan District, Yunnan Province, China. Phylogenetic analysis indicated that strain SYP-A7185 exhibited a 99.78% similarity to Streptomyces rosealbus YIM 31634T. The complete genome of Streptomyces sp. SYP-A7185 harbored 26 putative biosynthetic gene clusters (BGCs) associated with secondary metabolite biosynthesis. By integrating genomic strategies and metabolites analysis, four new nonclassical angucyclin(on)e derivatives (1, 3, 4, and 7) and three known compounds (2, 5, and 6) were identified. Characterization of BGC-14 as the angucyclin(on)es (Agn) biosynthetic gene cluster, together with the reconstruction of the biosynthetic pathway, highlighted the significant involvement of oxidoreductases AgnO1–AgnO7 in synthesizing compounds 1–7. Strikingly, this particular angucyclin(on)e biosynthetic gene cluster exhibited an uncommon occurrence of six glycosyltransferases AgnGT1–AgnGT6. The identification of these biosynthetic elements significantly expands the genetic resource available for angucyclin(on)e biosynthesis, providing valuable tools for targeted genetic manipulation and pathway engineering. Furthermore, cytotoxicity and antimicrobial assays showed that compounds 1–3 exhibited moderate antiproliferative effects, while compound 4 demonstrated moderate antimicrobial activity against Staphylococcus aureus and Klebsiella pneumoniae. The experimental findings underscore the diversity of angucyclin(on)e derivatives and their biological properties, providing valuable insights for future research and exploration.