2,2-Dimethyl-3-hydroxy-4-(1'-angeloyloxy)-6-acetylchromane is a natural product isolated from that exhibits inhibitory activity against yeast α-glucosidase. Initially, its structure was proposed to be 4-hydroxy-3-(()-1'-angeloyloxy-()-2',3'-epoxy-3'-methyl)butylacetophenone with an epoxide, but the structure was later revised to 2,2-dimethyl-3-hydroxy-4-(1-angeloyloxy)-6-acetylchromane. In this study, we present a total synthesis of 2,2-dimethyl-3-hydroxy-4-(1'-angeloyloxy)-6-acetylchromane from and its stereoisomers.
View Article and Find Full Text PDFSome members of the human gut microbiota profoundly influence their host's physiology, health, and therapeutic responses, but the responsible molecules and mechanisms are largely unknown. As part of a project to identify immunomodulators produced by gut microbes, we analyzed the metabolome of , an actinomycete that figures prominently in numerous association studies. The associations are typically positive correlations of with pro-inflammatory responses and undesirable outcomes, but an association with favorable responses to PD-1/PD-L1 cancer immunotherapy is a notable exception.
View Article and Find Full Text PDFTargeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency.
View Article and Find Full Text PDFDracaeconolide B (), a naturally occurring homoisoflavane, was isolated from the red resin of . Efforts have been made to elucidate the exact structure of compound since it was confirmed that dracaeconolide B did not contain a 7-hydroxy-5,8-dimethoxy moiety. The structure of dracaeconolide B was revised by synthesis of three homoisoflavanes containing a 5,6,7-trioxygenated moiety each and analysis by NMR spectroscopy.
View Article and Find Full Text PDFThree new secondary metabolites, actinoflavosides B-D (-), were discovered in the culture broth of two actinomycete strains (JML48 and JMS33) that were isolated from tidal mudflat sediment in Muan, Republic of Korea. The planar structures of the actinoflavosides were elucidated by MS, UV, and NMR analyses. The stereochemistry of an aminosugar, 2,3,6-trideoxy-3-amino-ribopyranoside in the actinoflavosides was determined by -based configuration analysis using values obtained from DQF-COSY experiments and modified Mosher's method.
View Article and Find Full Text PDFMultiple studies have established associations between human gut bacteria and host physiology, but determining the molecular mechanisms underlying these associations has been challenging. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favourable outcomes to checkpoint blockade in cancer immunotherapy and homeostatic immunity. Here we report the identification of a lipid from A.
View Article and Find Full Text PDFTwo new lipo-decapeptides, namely taeanamides A and B ( and ), were discovered from the Gram-positive bacterium sp. AMD43, which was isolated from a mudflat sample from Anmyeondo, Korea. The exact molecular masses of and were revealed by high-resolution mass spectrometry, and the planar structures of and were elucidated using NMR spectroscopy.
View Article and Find Full Text PDFMohangamide A is a pseudo-dimeric nonribosomal peptide biosynthesized along with its monomer, WS9326A, and is expected to be formed by the head-to-tail cyclodimerization of linear WS9326A and another identical peptide chain with a different acyl side chain. experiments with the -acetylcysteamine thioesters of the corresponding monomeric intermediates and thioesterase domains of sp. SNM55 and showed that this cyclodimerization reaction is directed by the substrate structures and occurs only with both linear intermediates.
View Article and Find Full Text PDFThe human immune system detects potentially pathogenic microbes with receptors that respond to microbial metabolites. While the overall immune signaling pathway is known in considerable detail, the initial molecular signals, the microbially produced immunogens, for important diseases like Lyme disease (LD) are often not well-defined. The immunogens for LD are produced by the spirochete , and a galactoglycerolipid () has been identified as a key trigger for the inflammatory immune response that characterizes LD.
View Article and Find Full Text PDFBile acids act as signaling molecules that regulate immune homeostasis, including the differentiation of CD4 T cells into distinct T cell subsets. The bile acid metabolite isoallolithocholic acid (isoalloLCA) enhances the differentiation of anti-inflammatory regulatory T cells (T cells) by facilitating the formation of a permissive chromatin structure in the promoter region of the transcription factor forkhead box P3 (Foxp3). Here, we identify gut bacteria that synthesize isoalloLCA from 3-oxolithocholic acid and uncover a gene cluster responsible for the conversion in members of the abundant human gut bacterial phylum Bacteroidetes.
View Article and Find Full Text PDFSHP2 is a protein tyrosine phosphatase that plays a critical role in the full activation of the Ras-MAPK pathway upon stimulation of receptor tyrosine kinases, which are frequently amplified or mutationally activated in human cancer. In addition, activating mutations in SHP2 result in developmental disorders and hematologic malignancies. Several allosteric inhibitors have been developed for SHP2 and are currently in clinical trials.
View Article and Find Full Text PDFSystematic inactivation of nonribosomal peptide synthetase (NRPS) domains and translocation of the thioesterase (TE) domain revealed several unprecedented nonlinear NRPS assembly processes during the biosynthesis of the cyclodepsipeptide WS9326A in Streptomyces sp. SNM55. First, two sets of type ΙΙ TE (TEΙΙ)-like enzymes mediate the shuttling of activated amino acids between two sets of stand-alone adenylation (A)-thiolation (T) didomain modules and an "A-less" condensation (C)-T module with distinctive specificities and flexibilities.
View Article and Find Full Text PDFDiatoms are photosynthetic microalgae that fix a significant fraction of the world's carbon. Because of their photosynthetic efficiency and high-lipid content, diatoms are priority candidates for biofuel production. Here, we report that sporulating Bacillus thuringiensis and other members of the Bacillus cereus group, when in co-culture with the marine diatom Phaeodactylum tricornutum, significantly increase diatom cell count.
View Article and Find Full Text PDFHerein is a report on the molecular exchange occurring between multilateral symbiosis partners-a tit-for-tat exchange that led to the characterization of two new metabolites, conocandin B (fungal-derived) and dentigerumycin F (bacterial-derived). The structures were determined by NMR, mass spectrometry, genomic analysis, and chemical derivatizations. Conocandin B exhibits antimicrobial activity against both the bacterial symbionts of fungus-growing ant and human pathogenic strains by selectively inhibiting FabH, thus disrupting fatty acid biosynthesis.
View Article and Find Full Text PDFThe intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility.
View Article and Find Full Text PDFRhizolutin (1) was discovered as a natural product of ginseng-rhizospheric Streptomyces sp. WON17. Its structure features an unprecedented 7/10/6-tricyclic dilactone carbon skeleton composed of dimethylcyclodecatriene flanked by a 7-membered and a 6-membered lactone ring based on spectroscopic analysis.
View Article and Find Full Text PDFChemical profiling of the sp. strain SUD119, which was isolated from a marine sediment sample collected from a volcanic island in Korea, led to the discovery of three new metabolites: donghaecyclinones A-C (-). The structures of - were found to be rearranged, multicyclic, angucyclinone-class compounds according to nuclear magnetic resonance (NMR) and mass spectrometry (MS) analyses.
View Article and Find Full Text PDFInflammation occurring within the transplanted organ from the time of harvest is an important stimulus of early alloimmune reactivity and promotes chronic allograft rejection. Chronic immune-mediated injury remains the primary obstacle to the long-term success of organ transplantation. However, organ transplantation represents a rare clinical setting in which the organ is accessible , providing an opportunity to use nanotechnology to deliver therapeutics directly to the graft.
View Article and Find Full Text PDFThe chemical analysis of a Streptomyces strain, from a Korean volcanic island, discovered new benz[ a]anthracene dimers linked by a thioether bond. The structures of donghaesulfins A and B (1 and 2) were elucidated by spectroscopic analysis including energy-dispersive X-ray. Their configurations were determined by ROESY NMR data, DP4 calculations, the modified Mosher's method, and ECD calculations.
View Article and Find Full Text PDFBombyxamycins A and B (1 and 2) were discovered from a silkworm gut Streptomyces bacterium. Spectroscopic analysis and multiple-step chemical derivatization identified them as 26-membered cyclic lactams with polyene features. Bombyxamycin A showed significant antibacterial and antiproliferative effects.
View Article and Find Full Text PDFMicrobial culture conditions in the laboratory, which conventionally involve the cultivation of one strain in one culture vessel, are vastly different from natural microbial environments. Even though perfectly mimicking natural microbial interactions is virtually impossible, the cocultivation of multiple microbial strains is a reasonable strategy to induce the production of secondary metabolites, which enables the discovery of new bioactive natural products. Our coculture of marine and strains isolated together from an intertidal mudflat led to discover a new metabolite, dentigerumycin E ().
View Article and Find Full Text PDFLC/MS-based chemical profiling of a ginseng farm soil-derived actinomycete strain, sp. BYK1371, enabled the discovery of two new cyclic heptapeptides, depsidomycins B and C ( and ), each containing two piperazic acid units and a formyl group at their -terminus. The structures of and were elucidated by a combination of spectroscopic and chemical analyses.
View Article and Find Full Text PDFWS9326H (1), a new cyclic peptide, was isolated from a mudflat-derived Streptomyces strain. Based on analysis by 1D/2D NMR, UV spectroscopy, and mass spectrometry, compound 1 was determined to have the gross structure of a cyclic heptapeptide bearing an unprecedented pyrazolone ring connected to a d-arabinitol via an amide bond. The absolute configuration of 1 was established by multistep chemical derivatizations, comprehensive NMR, and LC/MS analyses of the derivatives and quantum mechanics-based computational methods.
View Article and Find Full Text PDFTotal synthesis of the proposed structure of baulamycin A was performed. The spectral properties of the synthetic compound differ from those reported for the natural product. On the basis of comprehensive NMR study, we proposed two other possible structures for natural baulamycin A.
View Article and Find Full Text PDFBased on profiles of secondary metabolites produced by marine bacteria obtained using LC/MS, succinilenes A-D (-), new triene polyols, were discovered from a culture of a strain SAK1, which was collected in the southern area of Jeju Island, Republic of Korea. The gross structures of - were primarily determined through analysis of NMR spectra. The double bond geometries of the succinilenes, which could not be established from conventional ¹H NMR spectra because of the highly overlapped olefinic signals, were successfully deciphered using the recently developed quantum-mechanics-driven ¹H iterative full spin analysis (QM-HiFSA).
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