Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nematode signaling molecules derived from multimodular assembly of primary metabolic building blocks.

ABSTRACT: In the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus, a new class of natural products based on modular assembly of primary-metabolism-derived building blocks control organismal development and behavior. We report identification and biological activities of the first pentamodular metabolite, pasa#9, and the 8-oxoadenine-containing npar#3 from P. pacificus. These structures suggest co-option of nucleoside and tryptophan metabolic pathways for the biosynthesis of endogenous metabolite libraries that transcend the dichotomy between "primary" and "secondary" metabolism.

SUBMITTER: Yim JJ

PROVIDER: S-EPMC4878434 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Nematode signaling molecules derived from multimodular assembly of primary metabolic building blocks.

Yim Joshua J JJ Bose Neelanjan N Meyer Jan M JM Sommer Ralf J RJ Schroeder Frank C FC

Organic letters 20150318 7

In the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus, a new class of natural products based on modular assembly of primary-metabolism-derived building blocks control organismal development and behavior. We report identification and biological activities of the first pentamodular metabolite, pasa#9, and the 8-oxoadenine-containing npar#3 from P. pacificus. These structures suggest co-option of nucleoside and tryptophan metabolic pathways for the biosynthesis of endoge ...[more]

PMID: 25782998

Similar Datasets

Metabolomics analysis: Finding out metabolic building blocks.

Project description:In this paper we propose a new methodology for the analysis of metabolic networks. We use the notion of strongly connected components of a graph, called in this context metabolic building blocks. Every strongly connected component is contracted to a single node in such a way that the resulting graph is a directed acyclic graph, called a metabolic DAG, with a considerably reduced number of nodes. The property of being a directed acyclic graph brings out a background graph topology that reveals the connectivity of the metabolic network, as well as bridges, isolated nodes and cut nodes. Altogether, it becomes a key information for the discovery of functional metabolic relations. Our methodology has been applied to the glycolysis and the purine metabolic pathways for all organisms in the KEGG database, although it is general enough to work on any database. As expected, using the metabolic DAGs formalism, a considerable reduction on the size of the metabolic networks has been obtained, specially in the case of the purine pathway due to its relative larger size. As a proof of concept, from the information captured by a metabolic DAG and its corresponding metabolic building blocks, we obtain the core of the glycolysis pathway and the core of the purine metabolism pathway and detect some essential metabolic building blocks that reveal the key reactions in both pathways. Finally, the application of our methodology to the glycolysis pathway and the purine metabolism pathway reproduce the tree of life for the whole set of the organisms represented in the KEGG database which supports the utility of this research.

| S-EPMC5426688 | biostudies-literature

The Metabolic Building Blocks of a Minimal Cell.

Project description:Defining the essential gene components for a system to be considered alive is a crucial step toward the synthesis of artificial life. Fifteen years ago, Gil and coworkers proposed the core of a putative minimal bacterial genome, which would provide the capability to achieve metabolic homeostasis, reproduce, and evolve to a bacterium in an ideally controlled environment. They also proposed a simplified metabolic chart capable of providing energy and basic components for a minimal living cell. For this work, we have identified the components of the minimal metabolic network based on the aforementioned studies, associated them to the KEGG database and, by applying the MetaDAG methodology, determined its Metabolic Building Blocks (MBB) and reconstructed its metabolic Directed Acyclic Graph (m-DAG). The reaction graph of this metabolic network consists of 80 compounds and 98 reactions, while its m-DAG has 36 MBBs. Additionally, we identified 12 essential reactions in the m-DAG that are critical for maintaining the connectivity of this network. In a similar manner, we reconstructed the m-DAG of JCVI-syn3.0, which is an artificially designed and manufactured viable cell whose genome arose by minimizing the one from Mycoplasma mycoides JCVI-syn1.0, and of "Candidatus Nasuia deltocephalinicola", the bacteria with the smallest natural genome known to date. The comparison of the m-DAGs derived from a theoretical, an artificial, and a natural genome denote slightly different lifestyles, with a consistent core metabolism. The MetaDAG methodology we employ uses homogeneous descriptors and identifiers from the KEGG database, so that comparisons between bacterial strains are not only easy but also suitable for many research fields. The modeling of m-DAGs based on minimal metabolisms can be the first step for the synthesis and manipulation of minimal cells.

| S-EPMC7824019 | biostudies-literature

Chiral perylene diimides: building blocks for ionic self-assembly.

Project description:A chiral perylene diimide building block has been prepared based on an amine derivative of the amino acid L-phenylalanine. Detailed studies were carried out into the self-assembly behaviour of the material in solution and the solid state using UV/Vis, circular dichroism (CD) and fluorescence spectroscopy. For the charged building block BTPPP, the molecular chirality of the side chains is translated into the chiral supramolecular structure in the form of right-handed helical aggregates in aqueous solution. Temperature-dependent UV/Vis studies of BTPPP in aqueous solution showed that the self-assembly behaviour of this dye can be well described by an isodesmic model in which aggregation occurs to generate short stacks in a reversible manner. Wide-angle X-ray diffraction studies (WXRD) revealed that this material self-organises into aggregates with ?-? stacking distances typical for ?-conjugated materials. TEM investigations revealed the formation of self-assembled structures of low order and with no expression of chirality evident. Differential scanning calorimetry (DSC) and polarised optical microscopy (POM) were used to investigate the mesophase properties. Optical textures representative of columnar liquid-crystalline phases were observed for solvent-annealed samples of BTPPP. The high solubility, tunable self-assembly and chiral ordering of these materials demonstrate their potential as new molecular building blocks for use in the construction of chiro-optical structures and devices.

| S-EPMC4973615 | biostudies-literature

Carbene derived diradicaloids - building blocks for singlet fission?

Project description:Organic singlet diradicaloids promise application in non-linear optics, electronic devices and singlet fission. The stabilization of carbon allotropes/cumulenes (C1, C2, C4) by carbenes has been equally an area of high activity. Combining these fields, we showed recently that carbene scaffolds allow as well for the design of diradicaloids. Herein, we report a comprehensive computational investigation (CASSCF/NEVPT2; fractional occupation DFT) on the electronic properties of carbene-bridge-carbene type diradicaloids. We delineate how to adjust the properties of these ensembles through the choice of carbene and bridge and show that already a short C2 bridge results in remarkable diradicaloid character. The choice of the carbene separately tunes the energies of the S1 and T1 excited states, whereas the bridge adjusts the overall energy level of the excited states. Accordingly, we develop guidelines on how to tailor the electronic properties of these molecules. Of particular note, fractional occupation DFT is an excellent tool to predict singlet-triplet gaps.

| S-EPMC6053972 | biostudies-literature

Self-assembly of collagen building blocks guided by electric fields.

Project description:Show me the way: protein building blocks are programmed to assemble hierarchically and yield a defined fiber morphology of micrometric length and precise nanometric diameter. The key step of this method is to align the building blocks with an AC field prior to assembly. The resulting protein nanofibers are straightforwardly integrated with the circuitry for potential applications in bionanotechnology.

| S-EPMC5412948 | biostudies-literature

Assembly of protein building blocks using a short synthetic peptide.

Project description:Combining proteins or their defined domains offers new enhanced functions. Conventionally, two proteins are either fused into a single polypeptide chain by recombinant means or chemically cross-linked. However, these strategies can have drawbacks such as poor expression (recombinant fusions) or aggregation and inactivation (chemical cross-linking), especially in the case of large multifunctional proteins. We developed a new linking method which allows site-oriented, noncovalent, yet irreversible stapling of modified proteins at neutral pH and ambient temperature. This method is based on two distinct polypeptide linkers which self-assemble in the presence of a specific peptide staple allowing on-demand and irreversible combination of protein domains. Here we show that linkers can either be expressed or be chemically conjugated to proteins of interest, depending on the source of the proteins. We also show that the peptide staple can be shortened to 24 amino acids still permitting an irreversible combination of functional proteins. The versatility of this modular technique is demonstrated by stapling a variety of proteins either in solution or to surfaces.

| S-EPMC3309608 | biostudies-literature

Modular assembly of protein building blocks to create precisely defined megamolecules.

Project description:Enzyme-promoted assembly: The construction of a hetero-bifunctional protein building block, HaloTag-cutinase, that reacts rapidly and selectively with a small-molecule linker is described. The step-wise combination of these building blocks generates a 300 kDa "megamolecule" with precisely defined domain orientation, connectivity, and composition.

| S-EPMC3804166 | biostudies-literature

In silico protein design by combinatorial assembly of protein building blocks.

Project description:Utilizing concepts of protein building blocks, we propose a de novo computational algorithm that is similar to combinatorial shuffling experiments. Our goal is to engineer new naturally occurring folds with low homology to existing proteins. A selected protein is first partitioned into its building blocks based on their compactness, degree of isolation from the rest of the structure, and hydrophobicity. Next, the protein building blocks are substituted by fragments taken from other proteins with overall low sequence identity, but with a similar hydrophobic/hydrophilic pattern and a high structural similarity. These criteria ensure that the designed protein has a similar fold, low sequence identity, and a good hydrophobic core compared with its native counterpart. Here, we have selected two proteins for engineering, protein G B1 domain and ubiquitin. The two engineered proteins share approximately 20% and approximately 25% amino acid sequence identities with their native counterparts, respectively. The stabilities of the engineered proteins are tested by explicit water molecular dynamics simulations. The algorithm implements a strategy of designing a protein using relatively stable fragments, with a high population time. Here, we have selected the fragments by searching for local minima along the polypeptide chain using the protein building block model. Such an approach provides a new method for engineering new proteins with similar folds and low homology.

| S-EPMC2286547 | biostudies-literature

Rational selection of building blocks for the assembly of bispecific antibodies.

Project description:Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembly of these chains is critical. Here, we describe Chain Selectivity Assessment (CSA), a high-throughput method to rationally select parental monoclonal antibodies (mAbs) to make bispecific antibodies requiring correct heavy/light chain pairing. By deploying CSA, we have successfully identified mAbs that exhibit a native preference toward cognate chain pairing that enables the production of hetero-IgGs without additional engineering. Furthermore, CSA also identified rare light chains (LCs) that permit positive binding of the non-cognate arm in the common LC hetero-IgGs, also without engineering. This rational selection of parental mAbs with favorable developability characteristics is critical to the successful development of bispecific molecules with optimal manufacturability properties.

| S-EPMC7808324 | biostudies-literature

Toward Controlled Hierarchical Heterogeneities in Giant Molecules with Precisely Arranged Nano Building Blocks.

Project description:Herein we introduce a unique synthetic methodology to prepare a library of giant molecules with multiple, precisely arranged nano building blocks, and illustrate the influence of minute structural differences on their self-assembly behaviors. The T8 polyhedral oligomeric silsesquioxane (POSS) nanoparticles are orthogonally functionalized and sequentially attached onto the end of a hydrophobic polymer chain in either linear or branched configuration. The heterogeneity of primary chemical structure in terms of composition, surface functionality, sequence, and topology can be precisely controlled and is reflected in the self-assembled supramolecular structures of these giant molecules in the condensed state. This strategy offers promising opportunities to manipulate the hierarchical heterogeneities of giant molecules via precise and modular assemblies of various nano building blocks.

| S-EPMC4827544 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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