Nyuzenamide C, an Antiangiogenic Epoxy Cinnamic Acid-Containing Bicyclic Peptide from a Riverine sp.

A new nonribosomal peptide, nyuzenamide C (), was discovered from riverine sediment-derived sp. DM14. Comprehensive analysis of the spectroscopic data of nyuzenamide C () revealed that has a bicyclic backbone composed of six common amino acid residues (Asn, Leu, Pro, Gly, Val, and Thr) and four nonproteinogenic amino acid units, including hydroxyglycine, β-hydroxyphenylalanine, -hydroxyphenylglycine, and 3,β-dihydroxytyrosine, along with 1,2-epoxypropyl cinnamic acid. The absolute configuration of was proposed by -based configuration analysis, the advanced Marfey's method, quantum mechanics-based DP4 calculations, and bioinformatic analysis of its nonribosomal peptide synthetase biosynthetic gene cluster. Nyuzenamide C () displayed antiangiogenic activity in human umbilical vein endothelial cells and induced quinone reductase in murine Hepa-1c1c7 cells.