Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A bicyclic S-adenosylmethionine regeneration system applicable with different nucleosides or nucleotides as cofactor building blocks.

ABSTRACT: The ubiquitous cofactor S-adenosyl-l-methionine (SAM) is part of numerous biochemical reactions in metabolism, epigenetics, and cancer development. As methylation usually improves physiochemical properties of compounds relevant for pharmaceutical use, the sustainable use of SAM as a methyl donor in biotechnological applications is an important goal. SAM-dependent methyltransferases are consequently an emerging biocatalytic tool for environmentally friendly and selective alkylations. However, SAM shows undesirable characteristics such as degradation under mild conditions and its stoichiometric use is economically not reasonable. Here, we report an optimised biomimetic system for the regeneration of SAM and SAM analogues consisting of effective nucleoside triphosphate formation and an additional l-methionine regeneration cycle without by-product accumulation. The bicyclic system uses seven enzymes, S-methylmethionine as methyl donor and a surplus of inorganic polyphosphate, along with catalytic amounts of l-methionine and cofactor building block reaching conversions of up to 99% (up to 200 turnovers). We also show that the cycle can be run with cofactor building blocks containing different purine and pyrimidine nucleobases, which can be fed in at the nucleoside or nucleotide stage. These alternative cofactors are in turn converted to the corresponding SAM analogues, which are considered to be a key for the development of bioorthogonal systems. In addition to purified enzymes, the bicyclic system can also be used with crude lysates highlighting its broad biocatalytic applicability.

SUBMITTER: Popadic D

PROVIDER: S-EPMC8190896 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Sensing metal ions with DNA building blocks: fluorescent pyridobenzimidazole nucleosides.

Project description:We describe novel fluorescent N-deoxyribosides (1 and 2) having 2-pyrido-2-benzimidazole and 2-quino-2-benzimidazole as aglycones. The compounds were prepared from the previously unknown heterocyclic precursors and Hoffer's chlorosugar, yielding alpha anomers as the chief products. X-ray crystal structures confirmed the geometry and showed that the pyridine and benzimidazole ring systems deviated from coplanarity in the solid state by 154 degrees and 140 degrees , respectively. In methanol compounds 1 and 2 had absorption maxima at 360 and 370 nm, respectively, and emission maxima at 494 and 539 nm. Experiments revealed varied fluorescence responses of the nucleosides to a panel of 17 monovalent, divalent, and trivalent metal ions in methanol. One or both of the nucleosides showed significant changes with 10 of the metal ions. The most pronounced spectral changes for ligand-nucleoside 1 included red shifts in fluorescence (Au(+), Au(3+)), strong quenching (Cu(2+), Ni(2+), Pt(2+)), and substantial enhancements in emission intensity coupled with red shifts (Ag(+), Cd(2+), Zn(2+)). The greatest spectral changes for ligand-nucleoside 2 included a red shift in fluorescence (Ag(+)), a blue shift (Cd(2+)), strong quenching (Pd(2+), Pt(2+)), and substantial enhancements in emission intensity coupled with a blue shift (Zn(2+)). The compounds could be readily incorporated into oligodeoxynucleotides, where an initial study revealed that they retained sensitivity to metal ions in aqueous solution and demonstrated possible cooperative sensing behavior with several ions. The two free nucleosides alone can act as differential sensors for multiple metal ions, and they are potentially useful monomers for contributing metal ion sensing capability to DNAs.

| S-EPMC2533741 | biostudies-literature

Tau-Cofactor Complexes as Building Blocks of Tau Fibrils.

Project description:The aggregation of the human tau protein into neurofibrillary tangles is directly diagnostic of many neurodegenerative conditions termed tauopathies. The species, factors and events that are responsible for the initiation and propagation of tau aggregation are not clearly established, even in a simplified and artificial in vitro system. This motivates the mechanistic study of in vitro aggregation of recombinant tau from soluble to fibrillar forms, for which polyanionic cofactors are the most commonly used external inducer. In this study, we performed biophysical characterizations to unravel the mechanisms by which cofactors induce fibrillization. We first reinforce the idea that cofactors are the limiting factor to generate ThT-active tau fibrils, and establish that they act as templating reactant that trigger tau conformational rearrangement. We show that heparin has superior potency for recruiting monomeric tau into aggregation-competent species compared to any constituent intermediate or aggregate "seeds." We show that tau and cofactors form intermediate complexes whose evolution toward ThT-active fibrils is tightly regulated by tau-cofactor interactions. Remarkably, it is possible to find mild cofactors that complex with tau without forming ThT-active species, except when an external catalyst (e.g., a seed) is provided to overcome the energy barrier. In a cellular context, we propose the idea that tau could associate with cofactors to form a metastable complex that remains "inert" and reversible, until encountering a relevant seed that can trigger an irreversible transition to ?-sheet containing species.

| S-EPMC6923735 | biostudies-literature

Prebiotic phosphorylation of 2-thiouridine provides either nucleotides or DNA building blocks via photoreduction.

Project description:Breakthroughs in the study of the origin of life have demonstrated how some of the building blocks essential to biology could have been formed under various primordial scenarios, and could therefore have contributed to the chemical evolution of life. Missing building blocks are then sometimes inferred to be products of primitive biosynthesis, which can stretch the limits of plausibility. Here, we demonstrate the synthesis of 2'-deoxy-2-thiouridine, and subsequently 2'-deoxyadenosine and 2-deoxyribose, under prebiotic conditions. 2'-Deoxy-2-thiouridine is produced by photoreduction of 2,2'-anhydro-2-thiouridine, which is in turn formed by phosphorylation of 2-thiouridine-an intermediate of prebiotic RNA synthesis. 2'-Deoxy-2-thiouridine is an effective deoxyribosylating agent and may have functioned as such in either abiotic or proto-enzyme-catalysed pathways to DNA, as demonstrated by its conversion to 2'-deoxyadenosine by reaction with adenine, and 2-deoxyribose by hydrolysis. An alternative prebiotic phosphorylation of 2-thiouridine leads to the formation of its 5'-phosphate, showing that hypotheses in which 2-thiouridine was a key component of early RNA sequences are within the bounds of synthetic credibility.

| S-EPMC6597365 | biostudies-literature

Synthesis of triamino acid building blocks with different lipophilicities.

Project description:To obtain different amino acids with varying lipophilicity and that can carry up to three positive charges we have developed a number of new triamino acid building blocks. One set of building blocks was achieved by aminoethyl extension, via reductive amination, of the side chain of ortnithine, diaminopropanoic and diaminobutanoic acid. A second set of triamino acids with the aminoethyl extension having hydrocarbon side chains was synthesized from diaminobutanoic acid. The aldehydes needed for the extension by reductive amination were synthesized from the corresponding Fmoc-L-2-amino fatty acids in two steps. Reductive amination of these compounds with Boc-L-Dab-OH gave the C4-C8 alkyl-branched triamino acids. All triamino acids were subsequently Boc-protected at the formed secondary amine to make the monomers appropriate for the N-terminus position when performing Fmoc-based solid-phase peptide synthesis.

| S-EPMC4397077 | biostudies-literature

Purines 2010: Adenine Nucleosides and Nucleotides in Biomedicine

Project description: Not available

| S-EPMC2908743 | biostudies-literature

Simultaneous Quantification of Nucleosides and Nucleotides from Biological Samples.

Project description:We report a reverse phase chromatography mass spectrometry (LC-MS) method for simultaneous quantification of nucleosides and nucleotides from biological samples, where compound identification was achieved by a tier-wise approach and compound quantification was achieved via external calibration. A total of 65 authentic standards of nucleosides and nucleotides were used for the platform development. The limit of detection (LOD) of those compounds ranged from 0.05 nmol/L to 1.25 ?mol/L, and their limit of quantification (LOQ) ranged from 0.10 nmol/L to 2.50 ?mol/L. Using the developed method, nucleosides and nucleotides from human plasma, human urine, and rat liver were quantified. Seventy-nine nucleosides and nucleotides were identified from human urine and 28 of them were quantified with concentrations of 13.0 nmol/L-151 ?mol/L. Fifty-five nucleosides and nucleotides were identified from human plasma and 22 of them were quantified with concentrations of 1.21 nmol/L-8.54 ?mol/L. Fifty-one nucleosides and nucleotides were identified from rat liver and 23 were quantified with concentrations of 1.03 nmol/L-31.7 ?mol/L. These results demonstrate that the developed method can be used to investigate the concentration change of nucleosides and nucleotides in biological samples for the purposes of biomarker discovery or elucidation of disease mechanisms.

| S-EPMC6520184 | biostudies-literature

Broadly Applicable Synthesis of Arylated Dithieno[3,2-b:2',3'-d]pyrroles as Building Blocks for Organic Electronic Materials.

Project description:A novel and versatile method for the N-arylation of dithieno[3,2-b:2',3'-d]pyrrole (DTP) is presented. By Pd- or Cu-catalyzed coupling a variety of arenes and acenes were directly attached at the DTP-nitrogen yielding a variety of functionalized DTPs. Investigations on optical and redox properties led to valuable structure-property relationships, which were corroborated by quantum chemical calculations. Further functionalization and elongation of the conjugation of an acceptor-substituted DTP was elaborated to result in complex cruciform-type donor-acceptor oligomers, which were investigated and implemented in single material organic solar cells.

| S-EPMC8456814 | biostudies-literature

Survey of ribose ring pucker of signaling nucleosides and nucleotides.

Project description:The ribose of protein-bound nucleosides and nucleotides displays preferred conformations (usually either North or South), which can be exploited to design enhanced analogs having chemically fixed conformations. We introduce a computational protocol for assembling data from the protein database (PDB) on the ribose and ribose-like conformation of small molecule ligands when complexed with purinergic signaling proteins (including receptors, enzymes and transporters, and related intracellular pathways). Some targets prefer exclusively North (adenosine and P2Y1 receptors, CD73, adenosine kinase ATP/ADP-binding site, adenosine deaminase), others prefer South (P2Y12 receptor, E-NTPDase2) or East (adenosine kinase substrates), while others (P2XRs) allow various conformations.

| S-EPMC7047539 | biostudies-literature

Bacterial cellulose spheroids as building blocks for 3D and patterned living materials and for regeneration.

Project description:Engineered living materials (ELMs) based on bacterial cellulose (BC) offer a promising avenue for cheap-to-produce materials that can be programmed with genetically encoded functionalities. Here we explore how ELMs can be fabricated in a modular fashion from millimetre-scale biofilm spheroids grown from shaking cultures of Komagataeibacter rhaeticus. Here we define a reproducible protocol to produce BC spheroids with the high yield bacterial cellulose producer K. rhaeticus and demonstrate for the first time their potential for their use as building blocks to grow ELMs in 3D shapes. Using genetically engineered K. rhaeticus, we produce functionalized BC spheroids and use these to make and grow patterned BC-based ELMs that signal within a material and can sense and report on chemical inputs. We also investigate the use of BC spheroids as a method to regenerate damaged BC materials and as a way to fuse together smaller material sections of cellulose and synthetic materials into a larger piece. This work improves our understanding of BC spheroid formation and showcases their great potential for fabricating, patterning and repairing ELMs based on the promising biomaterial of bacterial cellulose.

| S-EPMC8377073 | biostudies-literature

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides.

Project description:Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-?-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-?-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-?-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility.

| S-EPMC5647706 | biostudies-other

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