Ohmyungsamycins A and B: Cytotoxic and Antimicrobial Cyclic Peptides Produced by <i>Streptomyces</i> sp. from a Volcanic Island

Abstract

Ohmyungsamycins A and B (<b>1</b> and <b>2</b>), which are new cyclic peptides, were isolated from a marine bacterial strain belonging to the <i>Streptomyces</i> genus collected from a sand beach on Jeju, a volcanic island in the Republic of Korea. Based on the interpretation of the NMR, UV, and IR spectroscopic and MS data, the planar structures of <b>1</b> and <b>2</b> were elucidated as cyclic depsipeptides bearing unusual amino acid units, including <i>N</i>-methyl-4-methoxytrytophan, β-hydroxyphenylalanine, and <i>N</i>,<i>N</i>-dimethylvaline. The absolute configurations of the α-carbons of the amino acid residues were determined using the advanced Marfey’s method. The configurations of the additional stereogenic centers at the β-carbons of the threonine, <i>N</i>-methylthreonine, and β-hydroxyphenylalanine units were assigned by GITC (2,3,4,6-tetra-<i>O</i>-acetyl-β-d-glucopyranosyl isothiocyanate) derivatization and the modified Mosher’s method. We have developed a new method utilizing PGME (phenylglycine methyl ester) derivatization coupled with chromatographic analysis to determine the absolute configuration of <i>N</i>,<i>N</i>-dimethylvaline. Our first successful establishment of the absolute configuration of <i>N</i>,<i>N</i>-dimethylvaline using PGME will provide a general and convenient analytical method for determining the absolute configurations of amino acids with fully substituted amine groups. Ohmyungsamycins A and B showed significant inhibitory activities against diverse cancer cells as well as antibacterial effects