Structure Determination of Bioactive Secondary Metabolites from Streptomyces spp. from a Saltern and the Dung Beetle, Copris tripartitus

Abstract

Part A. Structure Determination of the New Bioactive Metabolites from Streptomyces spp. in a Korea Saltern Microbial natural products have been proven to be a prolific source of novel therapeutic agents that have demonstrated significant activities in various pathological conditions including cancer, viral infection, inflammation, analgesia, and immune modulation. Halophilic Streptomyces have not been studied in the search of new secondary metabolites produced by bacteria adapted to hyper-saline environments. The secondary metabolites produced by adaptive Streptomyces have been expected to have new carbon skeleton for bioactivity of metabolites. Chemical studies of selected two halophilic strains lead to isolation of 12 novel compounds and 2 known compounds. These compounds have been structurally elucidated by combined spectroscopic methods and chemical analysis. The structures of 12 new compounds are belonged to various structural classes and have been derived from various biogenetic origins. Salternamides A-E, the first secondary metabolites discovered from saltern-derived actinomycetes, were isolated from a halophilic Streptomyces strain isolated from a saltern on Shinui Island in the Republic of Korea. Salternamide A, which is the first chlorinated compound in the manumycin family, exhibited potent cytotoxicity against a human colon cancer cell line (HCT116) and a gastric cancer cell line (SNU638) with submicromolar IC50 values. Xiamycins C-E, were isolated from a Streptomyces sp. (#HK18) culture inhabiting the topsoil in a Korean solar saltern. Xiamycin D shows the potential of indolo-sesquiterpenoids as new and promising chemical skeletons against Porcine Epidemic Diarrhea Virus-related viruses. Starkmycins A-D, the secondary metabolites discovered from saltern-derived actinomycetes, were isolated from a halophilic Streptomyces strain isolated from a saltern on Shinui Island in Korea.

Part B. Structure Determination of the New Bioactive Metabolites from Streptomyces sp. from the Dung Beetle, Copris tripartitus Investigation of the bacterial symbionts of eukaryotic hosts has become a powerful approach for the discovery of new chemical entities. In particular, insects, the phylogenetic group with the most biodiversity on Earth, host numerous chemically prolific bacteria. The bacteria associated with the dung beetle Copris tripartitus Waterhouse have been investigated in the search for new chemotypes because its system comprises extensive microbial communities that possibly originated from the feces of herbivores, which the beetle utilizes for feeding and making brood balls. The purpose of this work is the investigation of new bioactive metabolites from a larva of Dung beetle, Copris tripartitus. Based upon chemical analysis and bioassay, novel substances from a larva of Dung beetle, Copris tripartitus have been isolated and demonstrated the biomedical potential as new drug candidates. Chemical studies of selected Streptomyces sp. lead to isolation of novel compound. This compound have been structurally elucidated by combined spectroscopic methods and crystallization analysis. These results strongly suggest that novel compound can specifically inhibit histone H3 lysine 9 demethylase (KDM4).