Facile and Scalable Route to Access Rare Deoxy Amino Sugars for Nonulosonic Acid Aldolase Biosynthesis.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC9245050 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:We report herein a one-pot four-enzyme approach for the synthesis of the rare sugars d-psicose, d-sorbose, l-tagatose, and l-fructose with aldolase FucA from a thermophilic source (Thermus thermophilus HB8). Importantly, the cheap starting material DL-GP (DL-glycerol 3-phosphate), was used to significantly reduce the synthetic cost.
| S-EPMC3445428 | biostudies-literature
Project description:2-Deoxy-D-ribose-5-phosphate aldolase (DERA) is a class I aldolase that offers access to several building blocks for organic synthesis. It catalyzes the stereoselective C-C bond formation between acetaldehyde and numerous other aldehydes. However, the practical application of DERA as a biocatalyst is limited by its poor tolerance towards industrially relevant concentrations of aldehydes, in particular acetaldehyde. Therefore, the development of proper experimental conditions, including protein engineering and/or immobilization on appropriate supports, is required. The present review is aimed to provide a brief overview of DERA, its history, and progress made in understanding the functioning of the enzyme. Furthermore, the current understanding regarding aldehyde resistance of DERA and the various optimizations carried out to modify this property are discussed.
| S-EPMC6244999 | biostudies-literature
Project description:Campylobacter jejuni and Campylobacter coli are the most common causes of bacterial gastroenteritis in the world. Ganglioside mimicry by C. jejuni lipooligosaccharide (LOS) is the triggering factor of Guillain-Barré syndrome (GBS), an acute polyneuropathy. Sialyltransferases from glycosyltransferase family 42 (GT-42) are essential for the expression of ganglioside mimics in C. jejuni Recently, two novel GT-42 genes, cstIV and cstV, have been identified in C. coli Despite being present in ∼11% of currently available C. coli genomes, the biological role of cstIV and cstV is unknown. In the present investigation, mutation studies with two strains expressing either cstIV or cstV were performed and mass spectrometry was used to investigate differences in the chemical composition of LOS. Attempts were made to identify donor and acceptor molecules using in vitro activity tests with recombinant GT-42 enzymes. Here we show that CstIV and CstV are involved in C. coli LOS biosynthesis. In particular, cstV is associated with LOS sialylation, while cstIV is linked to the addition of a diacetylated nonulosonic acid residue.IMPORTANCE Despite the fact that Campylobacter coli a major foodborne pathogen, its glycobiology has been largely neglected. The genetic makeup of the C. coli lipooligosaccharide biosynthesis locus was largely unknown until recently. C. coli harbors a large set of genes associated with lipooligosaccharide biosynthesis, including genes for several putative glycosyltransferases involved in the synthesis of sialylated lipooligosaccharide in Campylobacter jejuni In the present study, C. coli was found to express lipooligosaccharide structures containing sialic acid and other nonulosonate acids. These findings have a strong impact on our understanding of C. coli ecology, host-pathogen interaction, and pathogenesis.
| S-EPMC6436355 | biostudies-literature
Project description:Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment-resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot-scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost.
| S-EPMC7383583 | biostudies-literature
Project description:Genes encoding 2-deoxy-d-ribose-5-phosphate aldolase (DERA) homologues from two hyperthermophiles, the archaeon Pyrobaculum aerophilum and the bacterium Thermotoga maritima, were expressed individually in Escherichia coli, after which the structures and activities of the enzymes produced were characterized and compared with those of E. coli DERA. To our surprise, the two hyperthermophilic DERAs showed much greater catalysis of sequential aldol condensation using three acetaldehydes as substrates than the E. coli enzyme, even at a low temperature (25 degrees C), although both enzymes showed much less 2-deoxy-d-ribose-5-phosphate synthetic activity. Both the enzymes were highly resistant to high concentrations of acetaldehyde and retained about 50% of their initial activities after a 20-h exposure to 300 mM acetaldehyde at 25 degrees C, whereas the E. coli DERA was almost completely inactivated after a 2-h exposure under the same conditions. The structure of the P. aerophilum DERA was determined by X-ray crystallography to a resolution of 2.0 A. The main chain coordinate of the P. aerophilum enzyme monomer was quite similar to those of the T. maritima and E. coli enzymes, whose crystal structures have already been solved. However, the quaternary structure of the hyperthermophilic enzymes was totally different from that of the E. coli DERA. The areas of the subunit-subunit interface in the dimer of the hyperthermophilic enzymes are much larger than that of the E. coli enzyme. This promotes the formation of the unique dimeric structure and strengthens the hydrophobic intersubunit interactions. These structural features are considered responsible for the extremely high stability of the hyperthermophilic DERAs.
| S-EPMC2168217 | biostudies-literature
Project description:Cyclopentane-1,3-diol (4b) has gained renewed attention as a potential building block for polymers and fuels because its synthesis from hemicellulose-derived 4-hydroxycyclopent-2-enone (3) was recently disclosed. However, cyclopentane-1,3-dione (4), which is a constitutional isomer of 3, possesses a higher chemical stability and can therefore afford higher carbon mass balances and higher yields of 4b in the hydrogenation reaction under more concentrated conditions. In this work, the hydrogenation of 4 into 4b over a commercial Ru/C catalyst was systematically investigated on a bench scale through kinetic studies and variation of reaction conditions. Herein, the temperature, H2-pressure, and the solvent choice were found to have significant effects on the reaction rate and suppression of undesired dehydration of 4. The cis-trans ratio of 4b is naturally generated as 7:3 in these reactions. However, at elevated reaction temperatures, 4b epimerizes, yielding more trans products. This effect was also studied and rationalized from a thermodynamic perspective using DFT. The combined optimized reaction conditions provided 78% yield for 4b, and successful applications to 8-fold scaled up reactions (40 g) and a substrate scope of several 1,3-diones demonstrate the general applicability of this catalytic approach.
| S-EPMC7893635 | biostudies-literature
Project description:A three-step synthesis of pseudoephenamine suitable for preparing multigram amounts of both enantiomers of the auxiliary from the inexpensive starting material benzil is described. The sequence involves synthesis of the crystalline monomethylimine derivative of benzil, reduction of that substance with lithium aluminum hydride, and resolution of pseudoephenamine with mandelic acid.
| S-EPMC3864801 | biostudies-literature
Project description:Reaction of the aluminum dialkynyl LAl(CCR)2 (L=N,N-chelate ligand and R=organic group) with B(C6 F5 )3 proceeds through an intermediate with Al⋅⋅⋅η2 -C≡C side-on coordination to form the alumoles (2, 4, 6). A distinctive reaction pattern indicates a new facile synthetic route to aluminum-containing heterocycles. The synthetic process is described, and the characterization of compounds and computational calculations were carried out. Furthermore, alumoles 2 and 4 exhibit an aggregation-induced emission (AIE) of the bright yellow fluorescence.
| S-EPMC7318123 | biostudies-literature
Project description:Cellulose nanofibril foams are cellulose-based porous materials with outstanding mechanical properties, resulting from the high strength-to-weight ratio of nanofibrils. Here we report the development of an optimized fabrication process for highly porous cellulose foams, based on a well-controlled freeze-thawing-drying (FTD) process at ambient pressure. This process enables the fabrication of foams with ultra-high porosity, up to 99.4%, density of 10 mg/cm3, and liquid (such as oil) absorption capacity of 100 L/kg. The proposed approach is based on the ice-templating of nanocellulose suspension in water, followed by thawing in ethanol and drying at environmental pressures. As such, the proposed fabrication route overcomes one of the major bottle-necks of the classical freeze-drying approach, by eliminating the energy-demanding vacuum drying step required to avoid wet foam collapse upon drying. As a result, the process is simple, environmentally friendly, and easily scalable. Details of the foam development fabrication process and functionalization are thoroughly discussed, highlighting the main parameters affecting the process, e.g., the concentration of nanocellulose and additives used to control the ice nucleation. The foams are also characterized by mechanical tests and oil absorption measurements, which are used to assess the foam absorption capability as well as the foam porosity. Compound water-in-oil drop impact experiments are used to demonstrate the potential of immiscible liquid separation using cellulose foams.
| S-EPMC6723185 | biostudies-other
Project description:Aspergillus fumigatus is a filamentous fungus that can cause severe respiratory disease in immunocompromised individuals. A putative sialidase from A. fumigatus was recently cloned and shown to be relatively poor in cleaving N-acetylneuraminic acid (Neu5Ac) in comparison with bacterial sialidases. Here we present the first crystal structure of a fungal sialidase. When the apo structure was compared with bacterial sialidase structures, the active site of the Aspergillus enzyme suggested that Neu5Ac would be a poor substrate because of a smaller pocket that normally accommodates the acetamido group of Neu5Ac in sialidases. A sialic acid with a hydroxyl in place of an acetamido group is 2-keto-3-deoxynononic acid (KDN). We show that KDN is the preferred substrate for the A. fumigatus sialidase and that A. fumigatus can utilize KDN as a sole carbon source. A 1.45-Å resolution crystal structure of the enzyme in complex with KDN reveals KDN in the active site in a boat conformation and nearby a second binding site occupied by KDN in a chair conformation, suggesting that polyKDN may be a natural substrate. The enzyme is not inhibited by the sialidase transition state analog 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) but is inhibited by the related 2,3-didehydro-2,3-dideoxy-D-glycero-D-galacto-nonulosonic acid that we show bound to the enzyme in a 1.84-Å resolution crystal structure. Using a fluorinated KDN substrate, we present a 1.5-Å resolution structure of a covalently bound catalytic intermediate. The A. fumigatus sialidase is therefore a KDNase with a similar catalytic mechanism to Neu5Ac exosialidases, and this study represents the first structure of a KDNase.
| S-EPMC3060529 | biostudies-literature