Bonnevillamides, Linear Heptapeptides Isolated from a Great Salt Lake-Derived Streptomyces sp.
Streptomyces sp. GSL-6B was isolated from sediment collected from the Great Salt Lake and investigation of its organic extract led to the isolation of three new linear heptapeptides, bonnevillamides A (1), B (2), and C (3). The bonnevillamides represent a new class of linear peptides featuring unprecedented non-proteinogenic amino acids. All three peptides contain the newly characterized bonnevillic acid moiety (3-(3,5-dichloro-4-methoxyphenyl)-2-hydroxyacrylic acid), as well as a heavily modified proline residue. Moreover, in bonnevillamide A, the terminal proline residue found in bonnevillamides B and C is replaced with 4-methyl-azetidine-2-carboxylic acid methyl ester. The structures of the three heptapeptides were elucidated by NMR, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and LC-MS/MS, and the absolute configuration of all proteinogenic amino acid residues were determined by advanced Marfey's method. Bonnevillamides A, B and C were evaluated for their effects on zebrafish embryo development. All three heptapeptides were shown to modulate heart growth and cardiac function, with bonnevillamide B having the most pronounced effect.
['Wu|Guangwei|G|', 'Nielson|Jason R|JR|', 'Peterson|Randall T|RT|', 'Winter|Jaclyn M|JM|']
D000818:Animals D004305:Dose-Response Relationship, Drug D004625:Embryo, Nonmammalian D060106:Lakes D007814:Larva D008958:Models, Molecular D015394:Molecular Structure D010455:Peptides D013302:Streptomyces D014589:Utah D015027:Zebrafish
heptapeptide Streptomyces sp. Great Salt Lake zebrafish azetidine hypersaline environment