Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rational Engineered C-Acyltransferase Transforms Sterically Demanding Acyl Donors.

ABSTRACT: The biocatalytic Friedel-Crafts acylation has been identified recently for the acetylation of resorcinol using activated acetic acid esters for the synthesis of acetophenone derivatives catalyzed by an acyltransferase. Because the wild-type enzyme is limited to acetic and propionic derivatives as the substrate, variants were designed to extend the substrate scope of this enzyme. By rational protein engineering, the key residue in the active site was identified which can be replaced to allow binding of bulkier acyl moieties. The single-point variant F148V enabled the transformation of previously inaccessible medium chain length alkyl and alkoxyalkyl carboxylic esters as donor substrates with up to 99% conversion and up to >99% isolated yield.

SUBMITTER: Zadlo-Dobrowolska A

PROVIDER: S-EPMC6996649 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rational Engineered C-Acyltransferase Transforms Sterically Demanding Acyl Donors.

Żądło-Dobrowolska Anna A Hammerer Lucas L Pavkov-Keller Tea T Gruber Karl K Kroutil Wolfgang W

ACS catalysis 20191227 2

The biocatalytic Friedel-Crafts acylation has been identified recently for the acetylation of resorcinol using activated acetic acid esters for the synthesis of acetophenone derivatives catalyzed by an acyltransferase. Because the wild-type enzyme is limited to acetic and propionic derivatives as the substrate, variants were designed to extend the substrate scope of this enzyme. By rational protein engineering, the key residue in the active site was identified which can be replaced to allow bind ...[more]

PMID: 32030315

Similar Datasets

Examining sterically demanding lysine analogs for histone lysine methyltransferase catalysis.

Project description:Methylation of lysine residues in histone proteins is catalyzed by S-adenosylmethionine (SAM)-dependent histone lysine methyltransferases (KMTs), a genuinely important class of epigenetic enzymes of biomedical interest. Here we report synthetic, mass spectrometric, NMR spectroscopic and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics studies on KMT-catalyzed methylation of histone peptides that contain lysine and its sterically demanding analogs. Our synergistic experimental and computational work demonstrates that human KMTs have a capacity to catalyze methylation of slightly bulkier lysine analogs, but lack the activity for analogs that possess larger aromatic side chains. Overall, this study provides an important chemical insight into molecular requirements that contribute to efficient KMT catalysis and expands the substrate scope of KMT-catalyzed methylation reactions.

| S-EPMC7048932 | biostudies-literature

Sterically Demanding Oxidative Amidation of ?-Substituted Malononitriles with Amines Using O2.

Project description:An efficient amidation method between readily available 1,1-dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of ?-peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile ?-carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.

| S-EPMC5094546 | biostudies-literature

Coupling of sterically demanding peptides by ?-thiolactone-mediated native chemical ligation.

Project description:The ligation of sterically demanding peptidyl sites such as those involving Val-Val and Val-Pro linkages has proven to be extremely challenging with conventional NCL methods that rely on exogenous thiol additives. Herein, we report an efficient ?-thiolactone-mediated additive-free NCL protocol that enables the establishment of these connections in good yield. The rapid NCL was followed by in situ desulfurization. Reaction rates between ?-thiolactones and conventional thioesters towards NCL were also investigated, and direct aminolysis was ruled out as a possible pathway. Finally, the potent cytotoxic cyclic-peptide axinastatin 1 has been prepared using the developed methodology.

| S-EPMC5892351 | biostudies-literature

Enhanced quantum yields by sterically demanding aryl-substituted ?-diketonate ancillary ligands.

Project description:Luminescent organometallic platinum(II) compounds are of interest as phosphors for organic light emitting devices. Their emissive properties can be tuned by variation of the ligands or by specific electron-withdrawing or electron-donating substituents. Different ancillary ligands can have a profound impact on the emission color and emission efficiency of these complexes. We studied the influence of sterically hindered, aryl-substituted ?-diketonates on the emission properties of C^C* cyclometalated complexes, employing the unsubstituted methyl-phenyl-imidazolium ligand. The quantum yield was significantly enhanced by changing the auxiliary ligand from acetylacetonate, where the corresponding platinum(II) complex shows only a very weak emission, to mesityl (mes) or duryl (dur) substituted acetylacetonates. The new complexes show very efficient emission with quantum yields >70% in the sky-blue spectral region (480 nm) and short decay times (<3 ?s).

| S-EPMC5870149 | biostudies-other

acyltransferase brachypodium-arabidopsis-Impact of Brachypodium acyl-transferases

Project description:ra15-03_oxpmt7-7 - acyltransferase brachypodium-arabidopsis - What biochemical function? What consequence on lignification when overexpressed in Arabidopsis thaliana? - Transcripts of Arabidopsis stem overexpressing an acyl transferase from Brachypodium are compared to wild type plants. The overexpression is under a specific promoter (C4H).

2018-10-01 | GSE120114 | GEO

Thioesters as Acyl Donors in Biocatalytic Friedel-Crafts-type Acylation Catalyzed by Acyltransferase from <i>Pseudomonas Protegens</i>.

Project description:Functionalization of aromatic compounds by acylation has considerable significance in synthetic organic chemistry. As an alternative to chemical Friedel-Crafts acylation, the C-acyltransferase from Pseudomonas protegens has been found to catalyze C-C bond formation with non-natural resorcinol substrates. Extending the scope of acyl donors, it is now shown that the enzyme is also able to catalyze C-S bond cleavage prior to C-C bond formation, thus aliphatic and aromatic thioesters can be used as acyl donors. It is worth to mention that this reaction can be performed in aqueous buffer. Identifying ethyl thioacetate as the most suitable acetyl donor, the products were obtained with up to >99 % conversion and up to 88 % isolated yield without using additional base additives; this represents a significant advancement to prior protocols.

| S-EPMC6686624 | biostudies-literature

Sterically Demanding Flexible Phosphoric Acids for Constructing Efficient and Multi‐Purpose Asymmetric Organocatalysts

Project description: Not available

| S-EPMC10947075 | biostudies-literature

Synthesis of Molybdenum and Tungsten Alkylidene Complexes That Contain Sterically Demanding Arenethiolate Ligands.

Project description:Imido alkylidene complexes of Mo and W and oxo alkylidene complexes of W that contain thiophenoxide ligands of the type S-2,3,5,6-Ph4C6H (STPP) and S-2,6-(mesityl)2C6H3 (SHMT = S-hexamethylterphenyl) have been prepared in order to compare their metathesis activity with that of the analogous phenoxide complexes. All thiolate complexes were significantly slower (up to ?10× slower) for the metathesis homocoupling of 1-octene or polymerization of 2,3-dicarbomethoxynorbornene, and none of them was Z-selective. The slower rates could be attributed to the greater ?-donating ability of a thiophenoxide versus the analogous phenoxide and consequently a higher electron density at the metal in the thiophenoxide complexes.

| S-EPMC4195517 | biostudies-other

Retooling Asymmetric Conjugate Additions for Sterically Demanding Substrates with an Iterative Data-Driven Approach.

Project description:The development of catalytic enantioselective methods is routinely carried out using easily accessible and prototypical substrates. This approach to reaction development often yields asymmetric methods that perform poorly using substrates that are sterically or electronically dissimilar to those used during the reaction optimization campaign. Consequently, expanding the scope of previously optimized catalytic asymmetric reactions to include more challenging substrates is decidedly nontrivial. Here, we address this challenge through the development of a systematic workflow to broaden the applicability and reliability of asymmetric conjugate additions to substrates conventionally regarded as sterically and electronically demanding. The copper-catalyzed asymmetric conjugate addition of alkylzirconium nucleophiles to form tertiary centers, although successful for linear alkyl chains, fails for more sterically demanding linear ?,?-unsaturated ketones. Key to adapting this method to obtain high enantioselectivity was the synthesis of modified phosphoramidite ligands, designed using quantitative structure-selectivity relationships (QSSRs). Iterative rounds of model construction and ligand synthesis were executed in parallel to evaluate the performance of 20 chiral ligands. The copper-catalyzed asymmetric addition is now more broadly applicable, even tolerating linear enones bearing tert-butyl ?-substituents. The presence of common functional groups is tolerated in both nucleophiles and electrophiles, giving up to 99% yield and 95% ee across 20 examples.

| S-EPMC7011729 | biostudies-literature

Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes.

Project description:The mammalian RBC lacks de novo lipid synthesis but maintains its membrane composition by rapid turnover of acyl moieties at the sn-2 position of phospholipids. Plasma-derived fatty acids are esterified to acyl-CoA by acyl-CoA synthetases and transferred to lysophospholipids by acyl-CoA:lysophospholipid acyltransferases. We report the characterization of three lysophosphatidylcholine (lysoPC) acyltransferases (LPCATs), products of the AYTL1, -2, and -3 genes. These proteins are three members of a LPCAT family, of which all three genes are expressed in an erythroleukemic cell line. Aytl2 mRNA was detected in mouse reticulocytes, and the presence of the product of the human ortholog was confirmed in adult human RBCs. The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes. Spliced variants of Aytl1, affecting a conserved catalytic motif, were identified. Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus. Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein.

| S-EPMC2224237 | 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