Nyuzenamide C, an Antiangiogenic Epoxy Cinnamic Acid-Containing Bicyclic Peptide from a Riverine <i>Streptomyces</i> sp.
Joon Soo An, Myoun‐Su Kim, Jae‐Ho Han, Sung Chul Jang, Ji Hyeon Im, Jinsheng Cui, Yeonjin Lee, Sang‐Jip Nam, Jongheon Shin, Sang Kook Lee, Yeo Joon Yoon, Dong‐Chan Oh
Abstract
A new nonribosomal peptide, nyuzenamide C (1), was discovered from riverine sediment-derived Streptomyces sp. DM14. Comprehensive analysis of the spectroscopic data of nyuzenamide C (1) revealed that 1 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, p-hydroxyphenylglycine, and 3,β-dihydroxytyrosine, along with 1,2-epoxypropyl cinnamic acid. The absolute configuration of 1 was proposed by J-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 (1) displayed antiangiogenic activity in human umbilical vein endothelial cells and induced quinone reductase in murine Hepa-1c1c7 cells.