The Discovery of Nocacyclomycins A–H, Cyclic Lipodepsipeptides from Nocardia sungurluensis YINM00009

Encouraging results after assessing the biosynthetic potential of Nocardia sungurluensis YINM00009 with the OSMAC strategy prompted its genomic investigation and the identification of biosynthetic gene clusters encoding putatively novel nonribosomal peptide natural products. Subsequent chemical investigation of this strain resulted in the isolation and characterization of eight new cyclic lipodepsipeptides, designated as nocacyclomycins A-H (1-8). Their structures, including absolute configurations, were unequivocally elucidated through comprehensive spectroscopic analysis, incorporating NMR, HRESIMS/MS, X-ray crystallography, and Marfey's method. Biological evaluation demonstrated that compounds 5 and 7 displayed significant cytotoxic activities against four human cancer cell lines (A549, HepG2, MDA-MB-231, and SW480) with IC₅₀ values ranging from 3.23 to 9.43 μM and exhibited negligible cytotoxicity in normal cells. A plausible biosynthetic pathway for nocacyclomycins 1-8 has been proposed based on bioinformatic analysis and the structural features of this family.