Dataset Information

Xanthohumol Activity-Based Probes Targeting Flavonoid Catabolism

ABSTRACT: Xanthohumol, the principle prenylflavonoid found in hops (Humulus lupulus), is a potential anti-inflammatory agent in the gut. To investigate the interactions between xanthohumol and catabolic gut bacteria, and its role in the anti-inflammatory pathway, a suite of xanthohumol-derived activity-based probes (ABPs) was synthesized and characterized in a model gut microbe. Through direct alkylation of both xanthohumol and structural isomer isoxanthohumol, an alkyne or diazirine-alkyne linker was attached to multiple alkylation sites to generate a suite of click chemistry enabled ABPs. LC-MS/MS data was analyzed with MaxQuant. This research was conducted by the "Discovery and Biological Signatures of Microbiome-Derived Xanthohumol Metabolites and their Role in Ameliorating Inflammatory Bowel Disease" project under the National Center for Complementary and Integrative Health (NCCIH) grant (R01AT010271). User facility data acquisition was performed under the EMSL project award 51663 (10.46936/reso.proj.2020.51663/60000245) at the Environmental Molecular Sciences Laboratory (https://ror.org/04rc0xn13), a DOE Office of Science User Facility sponsored by the Biological and Environmental Research program under Contract No. DE-AC05-76RL01830.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Eubacterium Ramulus (ncbitaxon:39490) Escherichia Coli (ncbitaxon:562)

SUBMITTER: Aaron Wright

PROVIDER: MSV000088789 | MassIVE | Fri Feb 04 20:24:00 GMT 2022

REPOSITORIES: MassIVE

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Affinity- and activity-based probes synthesized from structurally diverse hops-derived xanthohumol flavonoids reveal highly varied protein profiling in <i>Escherichia coli</i>.

Webber Lucas C LC Anderson Lindsey N LN Paraiso Ines L IL Metz Thomas O TO Bradley Ryan R Stevens Jan F JF Wright Aaron T AT

RSC advances 20231011 42

Xanthohumol, the principle prenylflavonoid found in hops (<i>Humulus lupulus</i>) and a reported anti-inflammatory agent, has great potential for pharmaceutical interventions related to inflammatory disorders in the gut. A suite of probes was prepared from xanthohumol and its structural isomer isoxanthohumol to enable profiling of both protein affinity binding and catalytic enzyme reactivity. The regiochemistry of the reactive group on the probes was altered to reveal how probe structure dictate ...[more]

PMID: 37829707

Similar Datasets

Project description:The phenotype of an organism results from its genotype and the influence of the environment throughout development. Even when using animals of the same genotype, independent studies may test animals of different phenotypes, resulting in poor replicability due to genotype-by-environment interactions. Thus, genetically defined strains of mice may respond differently to experimental treatments depending on their rearing environment. However, the extent of such phenotypic plasticity and its implications for the replicability of research findings have remained unknown. Here, we examined the extent to which common environmental differences between animal facilities modulate the phenotype of genetically homogeneous (inbred) mice. We conducted a comprehensive multi-center study, whereby inbred C57BL/6J mice from a single breeding cohort were allocated to and reared in five different animal facilities throughout early life and adolescence, before being transported to a single test laboratory. We found persistent effects of the rearing facility on the composition and heterogeneity of the gut microbial community. These effects were paralleled by persistent differences in body weight and in the behavioural phenotype of the mice. Furthermore, we show that environmental variation among animal facilities is strong enough to influence epigenetic patterns in neurons at the level of chromatin organization. We detected changes in chromatin organization in the regulatory regions of genes involved in nucleosome assembly, neuronal differentiation, synaptic plasticity and regulation of behaviour. Our findings demonstrate that common environmental differences between animal facilities may produce facility-specific phenotypes, from the molecular to the behavioural level. Furthermore, they highlight an important limitation of inferences from single-laboratory studies and thus argue that study designs should take environmental background into account to increase the robustness and replicability of findings.

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).