Structure determination of new bioactive secondary metabolites from Streptomyces, Actinomdaura, and Deinococcus bacteria

Abstract

1. Suncheonoside A-D, benzothioate glycoside from marine-derived Streptomyces sp. <br/> A marine-derived Streptomyces strain, SSC21, was isolated from the sediment of Suncheon Bay, Republic of Korea. Chemical analysis of the bacterial strain resulted in the isolation of four new metabolites, suncheonosides A-D (1-4), each bearing a sulfur atom. The planar structures of the suncheonosides were identified as hexa-substituted benzothioate glycosides by combined spectroscopic analyses. Analysis of the configuration of the sugar moieties based on ROESY NMR correlations, 1-bond 1H-13C coupling constant analysis, and chemical derivatizations elucidated that the suncheonosides incorporate only L-rhamnose. Suncheonosides A, B, and D promoted adiponectin production in a concentration-dependent manner during adipogenesis in human mesenchymal stem cells, suggesting anti-diabetic potential.<br/> <br/> 2. JS8 A and B, novel bacterial flavonoid, from Streptomyces sp. associated with white grub Protaetia brevitarsis seulensis. <br/> Investigation of secondary metabolites of bacteria associated with eukaryotic hosts has become a promising approach to discover novel bioactive compounds. In search for new bioactive chemotypes, I have been focusing on secondary metabolites of bacterial strains associated in the gut of a white grub of Protaetia brevitarsis seulensis. The secondary metabolite profiles of the 80 actinobacterial strains isolated from the gut of a P. brevitarsis grub were chemically analyzed by LC/MS. This chemical analysis led to the discovery of two new flavonoid-like compounds, which are dominantly found in plants but really uncommon as bacterial metabolites. The epimeric compounds JS8A and B (6-7) were purified by HPLC using a chiral column (a polysaccharide-based immobilizing cellulose to silica gel). Their structures were determined mainly by spectroscopic analysis of NMR and mass data. The absolute configurations were established by time-controlled acetylation followed by the application of the modified Moshers method using MTPA. Moreover, the comparative full genome analysis of the strain JS8 and the producer (CNB-689) of actionflavoside, will be discussed along with their structures.<br/> <br/> 3. Actinomadurol, an antibacterial norditerpenoid from a rare actinomycete, Actinomadura sp. KC-191<br/> A new secondary metabolite, actinomadurol (13), was isolated along with the known compound JBIR-65 (14) from a rare actinomycete, Actinomadura strain KC 191. The structure of 13 was established as a rare member of the bacterial C-19 norditerpenoid class by NMR data and ECD calculations. The absolute configuration of 14, which was previously reported without stereochemical analysis, was determined by using the modified Moshers method and ECD calculations. Actinomadurol (13) exhibited potent antibacterial activity against pathogenic strains, such as Staphylococcus aureus, Kocuria rhizophila and Proteus hauseri (MIC = 0.39 ~ 0.78 g/mL), whereas JBIR-65 (14) showed no antibacterial activity.<br/> <br/> 4. Deinococcucins A−D, aminoglycolipids from Deinococcus sp., a gut bacterium of the carpenter ant Camponotus japonicus. <br/> Four new aminoglycolipids, deinococcucins A-D (18-21), were discovered from a Deinococcus sp. strain isolated from the gut of queen carpenter ants, Camponotus japonicus. The structures of deinococcucins A-D were elucidated as a combination of N-acetyl glucosamine, 2,3-dihydroxypropanoic acid, and an alkyl amine with a C16 or C17 hydrocarbon chain primarily based on 1D and 2D nuclear magnetic resonance (NMR) and mass spectroscopic data. The exact location of the olefinic double bond in deinococcucins C-D (20-21) was assigned based on the liquid chromatography-mass spectroscopy (LC/MS) data obtained after olefin metathesis. The absolute configurations of the N-acetyl glucosamine and 2,3-dihydroxy moieties were determined through gas chromatography-mass spectroscopy (GC/MS) analysis of authentic samples and phenylglycine methyl ester (PGME)-derivatized products, respectively. Deinococcucins A and C displayed significant induction of quinone reductase in murine Hepa-1c1c7 cells.<br/>