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

Abstract

Ohmyungsamycins A and B (1 and 2), which are new cyclic peptides, were isolated from a marine bacterial strain belonging to the Streptomyces 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 1 and 2 were elucidated as cyclic depsipeptides bearing unusual amino acid units, including N-methyl-4-methoxytrytophan, β-hydroxyphenylalanine, and N,N-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, N-methylthreonine, and β-hydroxyphenylalanine units were assigned by GITC (2,3,4,6-tetra-O-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 N,N-dimethylvaline. Our first successful establishment of the absolute configuration of N,N-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.

Ohmyungsamycins promote antimicrobial responses through autophagy activation via AMP-activated protein kinase pathway

“…OMS-A and OMS-B have inhibitory activities against Bacillus subtilis , Kocuria rhizophila , and Proteus hauseri 16 . To examine the anti-mycobacterial effects of OMS-A and OMS-B, we first assessed the antibacterial properties of OMS-A and OMS-B against Mtb.…”

“…We previously reported that ohmyungsamycins (OMS) A and B are novel cyclic peptides that were isolated from a marine bacterial strain belonging to the Streptomyces genus collected from Jeju Island in Korea 16 . We previously showed that OMS-A and -B are cyclic peptides that exhibit inhibitory effects against a diverse range of cancer cells and bacteria such as Bacillus subtilis , Kocuria rhizophila , and Proteus hauseri 16 .…”

“…We previously showed that OMS-A and -B are cyclic peptides that exhibit inhibitory effects against a diverse range of cancer cells and bacteria such as Bacillus subtilis , Kocuria rhizophila , and Proteus hauseri 16 . In this study, we demonstrated that OMS-A and -B are robust activators of autophagy that lead to antimicrobial responses against Mtb.…”

Salternamide E from a Saltern-derived Marine ActinomyceteStreptomycessp.

“…6 New cytotoxic and antimicrobial cyclic peptides, ohmyungsamycins A and B, were discovered from a seashore-derived actinomycete. 7 Our LC/MS-based chemical analysis also led to the discovery of a new benzofuran glycoside and indole alkaloids from a sponge-associated Amycolatopsis sp. 8 Novel dilactone-tethered pseudo-dimeric peptides, mohangamides A and B, which inhibit Candida albicans isocitrate lyase, were discovered from a mudflatderived Streptomyces sp.…”

QM-HiFSA-Aided Structure Determination of Succinilenes A–D, New Triene Polyols from a Marine-Derived Streptomyces sp.

“…As part of our efforts to discover new bioactive natural products, we have been investigating the chemistry of actinobacteria derived from marine and saline environments including salterns [5,6,7], intertidal zones [8,9,10,11], and deep-sea sediments [12]. In our previous reports, novel bioactive secondary metabolites were mainly identified through the chemical profiling of bacterial secondary metabolites by LC/MS analysis.…”