Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GenoChemetic Strategy for Derivatization of the Violacein Natural Product Scaffold.

ABSTRACT: Natural products and their analogues are often challenging to synthesize due to their complex scaffolds and embedded functional groups. Solely relying on engineering the biosynthesis of natural products may lead to limited compound diversity. Integrating synthetic biology with synthetic chemistry allows rapid access to much more diverse portfolios of xenobiotic compounds, which may accelerate the discovery of new therapeutics. As a proof-of-concept, by supplementing an Escherichia coli strain expressing the violacein biosynthesis pathway with 5-bromo-tryptophan in vitro or tryptophan 7-halogenase RebH in vivo, six halogenated analogues of violacein or deoxyviolacein were generated, demonstrating the promiscuity of the violacein biosynthesis pathway. Furthermore, 20 new derivatives were generated from 5-brominated violacein analogues via the Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein we demonstrate a flexible and rapid approach to access a diverse chemical space that can be applied to a wide range of natural product scaffolds.

SUBMITTER: Lai HE

PROVIDER: S-EPMC8609527 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Selective molecular sequestration with concurrent natural product functionalization and derivatization: from crude natural product extracts to a single natural product derivative in one step.

Project description:A resin-bound nitroso compound sequestered a single unexpected component from crude plant seed extracts. Several plants, including Piper nigrum, Eugenia caryophyllata, and Pimenta dioica, were extracted with organic solvent in the presence of a nitroso-containing resin. The nitroso resin selectively sequestered a single compound, β-caryophyllene, via a chemo- and regioselective ene reaction. The ene product was released from the resin, and proper selection of the solid-phase linker and cleavage cocktail allowed concomitant further transformation of the primary ene product to a novel functionalized polycycle. Preliminary studies indicate that the new hydroxylamine-containing natural product derivatives have antibiotic activity.

| S-EPMC3241990 | biostudies-literature

The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8.

Project description:Violacein, an indole-derived, purple-colored natural pigment isolated from Chromobacterium violaceum has shown multiple biological activities. In this work, we studied the effect of violacein in different immune cell lines, namely THP-1, MonoMac 6, ANA-1, Raw 264.7 cells, as well as in human peripheral blood mononuclear cells (PBMCs). A stimulation of TNF-α production was observed in murine macrophages (ANA-1 and Raw 264.7), and in PBMCs, IL-6 and IL-1β secretion was detected. We obtained evidence of the molecular mechanism of activation by determining the mRNA expression pattern upon treatment with violacein in Raw 264.7 cells. Incubation with violacein caused activation of pathways related with an immune and inflammatory response. Our data utilizing TLR-transfected HEK-293 cells indicate that violacein activates the human TLR8 (hTLR8) receptor signaling pathway and not human TLR7 (hTLR7). Furthermore, we found that the immunostimulatory effect of violacein in PBMCs could be suppressed by the specific hTLR8 antagonist, CU-CPT9a. Finally, we studied the interaction of hTLR8 with violacein in silico and obtained evidence that violacein could bind to hTLR8 in a similar fashion to imidazoquinoline compounds. Therefore, our results indicate that violacein may have some potential in contributing to future immune therapy strategies.

| S-EPMC6754391 | biostudies-literature

Synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold.

Project description:A short practical synthesis of a new natural product based scaffold (6), based on antitrypanosomal and antimalarial compounds isolated from different Plakortis species is described. The scaffold contains a peroxide unit that is surprisingly stable to chemical manipulation elsewhere in the molecule, enabling it to be elaborated into a small library of derivatives. It is stable to ozonolysis, reductive work-up with dimethylsulfide and the Wittig reaction with stabilized phosphorus ylides. The scaffold along with its Wittig analogues has displayed low to sub-micro molar (0.2-3.3 μM) antitrypanosomal activity.

| S-EPMC3228865 | biostudies-literature

A novel natural product inspired scaffold with robust neurotrophic, neurogenic and neuroprotective action.

Project description:In search for drugs to treat neuropsychiatric disorders wherein neurotrophic and neurogenic properties are affected, two neurotrophically active small molecules specially crafted following natural product leads based on 2-oxa-spiro[5.5]-undecane scaffold, have been thoroughly evaluated for their neurotrophic, neurogenic and neuroprotective potential in ex vivo primary culture and in vivo zebrafish and mouse models. The outcome of in vivo investigations suggest that one of these molecules is more neurotrophic than neurogenic while the other one is more neurogenic than neurotrophic and the former exhibits remarkable neuroprotection in a mouse acute ischemic stroke model. The molecular mechanisms of action of these compounds appear to be through the TrkB-MEK-ERK-CREB-BDNF pathway as pre-treatment with neurotrophin receptor TrkB inhibitor ANA-12 and MEK inhibitor PD98059 attenuates the neurotrophic action of compounds.

| S-EPMC4585672 | biostudies-literature

Synthesis of 2-BMIDA Indoles via Heteroannulation: Applications in Drug Scaffold and Natural Product Synthesis.

Project description:A Pd-catalyzed heteroannulation approach for the synthesis of C2 borylated indoles is reported. The process allows access to highly functionalized 2-borylated indole scaffolds with complete control of regioselectivity. The utility of the process is demonstrated in the synthesis of borylated sulfa drugs and in the concise synthesis of the Aspidosperma alkaloid Goniomitine.

| S-EPMC9062883 | biostudies-literature

Enantioselective Synthesis of a Tricyclic, sp3 -Rich Diazatetradecanedione: an Amino Acid-Based Natural Product-Like Scaffold.

Project description:6-, 7-, and 8-membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.04,?9 ]-tetradecanedione scaffold. Advanced building blocks based on d-aspartic acid and l-pyroglutamic acid were combined by a sp3 -sp2 Negishi coupling. A carbamate-guided syn-diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one-pot hydroxyl-group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp3 -rich tricycle. The final compound is a substrate mimic of peptidyl-prolyl cis-trans isomerases featuring a locked trans-amide bond. Cheminformatic analysis of 179?virtual derivatives indicates favourable physicochemical properties and drug-like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506-binding protein 12.

| S-EPMC7187416 | biostudies-literature

Natural Product Based 6-Hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium Scaffold as A New Antifungal Template.

Project description:Synthetic analogues of the marine-derived class of natural products phloeodictines have been prepared and exhibited potent in vitro fungicidal activities against a broad array of fungal pathogens including drug resistant strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural moiety with a C12 to C16 aliphatic side chain at C-6 has been shown to be the antifungal pharmacophore and may serve as a new antifungal template for further lead optimization.

| S-EPMC3129868 | biostudies-literature

Applying a Chemogeographic Strategy for Natural Product Discovery from the Marine Cyanobacterium Moorena bouillonii.

Project description:The tropical marine cyanobacterium Moorena bouillonii occupies a large geographic range across the Indian and Western Tropical Pacific Oceans and is a prolific producer of structurally unique and biologically active natural products. An ensemble of computational approaches, including the creation of the ORCA (Objective Relational Comparative Analysis) pipeline for flexible MS1 feature detection and multivariate analyses, were used to analyze various M. bouillonii samples. The observed chemogeographic patterns suggested the production of regionally specific natural products by M. bouillonii. Analyzing the drivers of these chemogeographic patterns allowed for the identification, targeted isolation, and structure elucidation of a regionally specific natural product, doscadenamide A (1). Analyses of MS2 fragmentation patterns further revealed this natural product to be part of an extensive family of herein annotated, proposed natural structural analogs (doscadenamides B-J, 2-10); the ensemble of structures reflect a combinatorial biosynthesis using nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) components. Compound 1 displayed synergistic in vitro cancer cell cytotoxicity when administered with lipopolysaccharide (LPS). These discoveries illustrate the utility in leveraging chemogeographic patterns for prioritizing natural product discovery efforts.

| S-EPMC7602127 | biostudies-literature

Natural Product Inspired Environmentally Friendly Strategy Based on Dopamine Chemistry toward Sustainable Marine Antifouling.

Project description:The combination of natural active antifouling composition and intelligent coatings has been regarded as a prospective approach to avoid marine biofouling. However, the relatively complex coating structure and the excessive rapid release of antifoulants maintain unresolved issues in their practical application. In this work, a novel environmentally friendly natural antifoulant (Stellera chamaejasme, SC) encapsulated in the polydopamine (PDA) microcapsule (SC@PDA) is prepared by emulsion interfacial polymerization and blended with the acrylate polymer to prepare a sustainable antifouling coating. Herein, the PDA shell acting as an "intelligent capsule" ensures the controlled release of the antifoulant SC, and the corresponding SC loading amount could be high up to 75.40%. As a model antifoulant, the impact of SC on the adsorption activity of the protein bovine serum albumin (BSA) is studied, as well as the settlement of presentative fouling communities (diatom Navicula sp. and red algae Porphyridium sp.) on the constructed coating. The experimental results demonstrate that the natural product SC integrated eco-friendly antifouling coating occupies the superior capacity of impeding the adsorption of both protein BSA and algae. Such antifoulant (SC) integrating with controlled release character is a great advance in terms of marine antifouling applications. It is, therefore, expected that this innovation will provide guiding significance for developing the next generation of antifouling techniques, especially in the field of marine antifouling.

| S-EPMC7469372 | biostudies-literature

High-throughput screening identifies a novel natural product-inspired scaffold capable of inhibiting Clostridioides difficile in vitro.

Project description:Clostridioides difficile is an enteric pathogen responsible for causing debilitating diarrhea, mostly in hospitalized patients. The bacterium exploits on microbial dysbiosis induced by the use of antibiotics to establish infection that ranges from mild watery diarrhea to pseudomembranous colitis. The increased prevalence of the disease accompanied by exacerbated comorbidity and the paucity of anticlostridial drugs that can tackle recurrence entails novel therapeutic options. Here, we report new lead molecules with potent anticlostridial activity from the AnalytiCon NATx library featuring natural product-inspired or natural product-derived small molecules. A high-throughput whole-cell-based screening of 5000 synthetic compounds from the AnalytiCon NATx library helped us identify 10 compounds capable of inhibiting the pathogen. Out of these 10 hits, we found 3 compounds with potent activity against C. difficile (MIC = 0.5-2 μg/ml). Interestingly, these compounds had minimal to no effect on the indigenous intestinal microbial species tested, unlike the standard-of-care antibiotics vancomycin and fidaxomicin. Further in vitro investigation revealed that the compounds were nontoxic to Caco-2 cell line. Given their potent anticlostridial activity, natural product-inspired scaffolds may suggest potential avenues that can address the unmet needs in preventing C. difficile mediated disease.

| S-EPMC8149678 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data