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

  • J Nat Prod. 2022 Apr 22;85(4):804-814. doi: 10.1021/acs.jnatprod.1c00837.
Joon Soo An  1 ,  Myoun-Su Kim  1 ,  Jaeho Han  1 ,  Sung Chul Jang  1 ,  Ji Hyeon Im  1 ,  Jinsheng Cui  1 ,  Yeonjin Lee  1 ,  Sang-Jip Nam  2 ,  Jongheon Shin  1 ,  Sang Kook Lee  1 ,  Yeo Joon Yoon  1 ,  Dong-Chan Oh  1
Affiliations
  • 1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
  • 2. Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
PMID: 35294831 DOI: 10.1021/acs.jnatprod.1c00837
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.