Project description:Untargeted-metabolomics LC-MS/MS analysis of commercial natural products pool, analyzed with different DDA settings with the objective to find the best one.
Project description:Natural products exhibit potential as candidates for developing multi-target agents for Alzheimer's disease treatment. The aim of this study is to utilize network-based medicine to identify novel natural products for Alzheimer's disease, and investigate their efficacy and mechanisms of action. In this study, we identified (-)-Vestitol and Salviolone as new potential natural products for treating Alzheimer's disease via an Alzheimer's disease-related pathway-gene network. Both natural products improved the cognition of APP/PS1 transgenic mice, reduced Aβ deposition, and lowered soluble toxic Aβ levels in the brain. Notably, a synergistic effect was observed when the two natural products were combined. Transcriptomic analysis and qRT-PCR experiments revealed that the synergistic mechanism of (-)-Vestitol and Salviolone combination is associated with the regulation of a broader range of AD-related pathways and genes, particularly the neuroactive ligand-receptor interaction pathway and calcium signaling pathway.
Project description:SDF-1 has been reported to trigger ADAMTS4,5 overexpression through activating CXCR4 signaling in chondrocytes. Here we described the transcriptional changes of SDF-1-treatment as well as natural products CXCR4 antagonists treatment.
Project description:We integrated quantitative proteomics and activity-based protein profiling (ABPP) approach to systematically elucidate the involved pathways and the covalent targets of natural products.
Project description:Anaerobic fungi (class Neocallimastigomycetes) thrive as low-abundance members of the herbivore digestive tract. The genomes of anaerobic gut fungi are poorly characterized and have not been extensively mined for the biosynthetic enzymes of natural products such as antibiotics. Here, we investigate the potential of anaerobic gut fungi to synthesize natural products that could regulate membership within the gut microbiome. Complementary 'omics' approaches were combined to catalog the natural products of anaerobic gut fungi from four different representative species: Anaeromyces robustus (A. robustus), Caecomyces churrovis (C. churrovis), Neocallimastix californiae (N. californiae), and Piromyces finnis (P. finnis). In total, 146 genes were identified that encode biosynthetic enzymes for diverse types of natural products, including nonribosomal peptide synthetases and polyketide synthases. In addition, N. californiae and C. churrovis genomes encoded seven putative bacteriocins, a class of antimicrobial peptides typically produced by bacteria. During standard laboratory growth on plant biomass or soluble substrates, 26% of total core biosynthetic genes in all four strains were transcribed. Across all four fungal strains, 30% of total biosynthetic gene products were detected via proteomics when grown on cellobiose. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) characterization of fungal supernatants detected 72 likely natural products from A. robustus alone. A compound produced by all four strains of anaerobic fungi was putatively identified as the polyketide-related styrylpyrone baumin. Molecular networking quantified similarities between tandem mass spectrometry (MS/MS) spectra among these fungi, enabling three groups of natural products to be identified that are unique to anaerobic fungi. Overall, these results support the finding that anaerobic gut fungi synthesize natural products, which could be harnessed as a source of antimicrobials, therapeutics, and other bioactive compounds. See publication: https://www.doi.org/10.1073/pnas.2019855118.
This research was performed under the Facilities Integrating Collaborations for User Science (FICUS) program (proposal:https://doi.org/10.46936/fics.proj.2018.50386/60000039) and used resources at the DOE Joint Genome Institute (https://ror.org/04xm1d337) and the Environmental Molecular Sciences Laboratory (https://ror.org/04rc0xn13), which are DOE Office of Science User Facilities operated under Contract Nos. DE-AC02-05CH11231 (JGI) and DE-AC05-76RL01830 (EMSL).