A Cyclohexapeptide and Its Rare Glycosides from Marine Sponge-Derived Streptomyces sp. OUCMDZ-4539

Pyridapeptide A (1), a cyclohexapeptide containing hexahydropyridazine-3-carboxylic acid (HPDA), 5-hydroxytetrahydropyridazine-3-carboxylic acid (γ-OH-TPDA), and (2S,3R,4E,6E)-2-amino-3-hydroxy-8-methylnona-4,6-dienoic acid residues, and its four glycopeptides, pyridapeptides B-E (2-5, respectively), were isolated from the fermentation broth of the marine sponge-derived Streptomyces sp. OUCMDZ-4539. Their structures were determined on the basis of spectroscopic analysis and chemical methods. Pyridapeptides B-E have one or more 2,3,6-trideoxyhexose sugar units glycosylated at the γ-OH-TPDA residue. The biosynthetic pathways were proposed on the basis of gene cluster analysis. Compounds 4 and 5, containing four sugar groups, displayed significant antiproliferative activity against five human cancer cell lines (PC9, MKN45, HepG2, HCT-116, and K562).