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1.
Org Lett ; 24(1): 158-163, 2022 01 14.
Article in English | MEDLINE | ID: mdl-34898224

ABSTRACT

Comprehensive analyses of the metabolite spectra of Aspergillus sp. EGF 15-0-3 under different culture conditions revealed the presence of unique environmental-induced metabolites exclusively from the rice medium. Subsequent target isolation afforded four unprecedented indole diketopiperazine-based hybrids with a pyrano[3',2':7,8]isochromeno[4,3-b]pyrazino[2,1-i]indole core (1 and 2) or a spiro[piperazine-2,2'-pyrano[3,4,5-de]chromene] scaffold (3 and 4). Putative biosynthetic pathways for 1-4, with Diels-Alder cycloadditions as key steps, were proposed. 1-4 exhibited selective cytotoxicities among several human cancer cells.

2.
Sci Rep ; 3: 1753, 2013.
Article in English | MEDLINE | ID: mdl-23628927

ABSTRACT

For biosynthesis of bacillamide C by Bacillus atrophaeus C89 associated with South China sea sponge Dysidea avara, it is hypothesized that decarboxylation from L-tryptophan to tryptamine could be performed before amidation by the downstream aromatic L-amino acid decarboxylase (AADC) to the non-ribosomal peptide synthetases (NRPS) gene cluster for biosynthesizing bacillamide C. The structural analysis of decarboxylases' known substrates in KEGG database and alignment analysis of amino acid sequence of AADC have suggested that L-tryptophan and L-phenylalanine are the potential substrates of AADC. The enzymatic kinetic experiment of the recombinant AADC proved that L-tryptophan is a more reactive substrate of AADC than L-phenylalanine. Meanwhile, the AADC-catalyzed conversion of L-tryptophan into tryptamine was confirmed by means of HPLC and LC/MS. Thus during bacillamide C biosynthesis, the decarboxylation of L-tryptophan to tryptamine is likely conducted first under AADC catalysis, followed by the amidation of tryptamine with the carboxylic product of NRPS gene cluster.


Subject(s)
Aromatic-L-Amino-Acid Decarboxylases/metabolism , Bacillus/metabolism , Tryptamines/biosynthesis , Amino Acid Sequence , Animals , Aromatic-L-Amino-Acid Decarboxylases/genetics , Bacillus/enzymology , Bacillus/genetics , Decarboxylation , Dysidea/genetics , Dysidea/metabolism , Molecular Sequence Data , Peptide Synthases/genetics , Peptide Synthases/metabolism , Phenylalanine/genetics , Phenylalanine/metabolism , Sequence Alignment , Thiazoles/metabolism , Tryptamines/metabolism , Tryptophan/genetics , Tryptophan/metabolism
3.
J Asian Nat Prod Res ; 15(1): 89-93, 2013.
Article in English | MEDLINE | ID: mdl-23324033

ABSTRACT

Aglinin A (1) is a mixture of C(24)-epimeric 20S,24-epoxy-24,25-dihydroxy-3,4-secodammar-4(28)-en-3-oic acid and present in plants of the family Meliaceae. The two epimers of 1 were resolved through an acetonide reaction, and the absolute configurations of two derivatives were deduced by the analysis of their (13)C NMR differences induced by γ-gauche or steric effect. Based on it, the (13)C NMR assignment of 24R-1 and 24S-1 was also established.


Subject(s)
Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Meliaceae/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purification , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Stereoisomerism , Triterpenes/pharmacology
5.
J Am Chem Soc ; 128(20): 6721-9, 2006 May 24.
Article in English | MEDLINE | ID: mdl-16704275

ABSTRACT

The major structural component of the cell wall of Mycobacterium tuberculosis is a lipidated polysaccharide, the mycoyl-arabinogalactan-peptidoglycan (mAGP) complex. This glycoconjugate plays a key role in the survival of the organism, and thus, enzymes involved in its biosynthesis have attracted attention as sites for drug action. At the core of the mAGP is a galactan composed of D-galactofuranose residues attached via alternating beta-(1-->5) and beta-(1-->6) linkages. A single enzyme, glfT, has been shown to synthesize both glycosidic linkages. We report here the first high-level expression and purification of glfT by expression of the Rv3808c gene in Escherichia coli C41(DE3). Following a three-step purification procedure, 3-7 mg of protein of >95% purity was isolated from each liter of culture. We subsequently probed the substrate specificity of glfT by evaluating a panel of potential mono- and oligosaccharide substrates and demonstrated, for the first time, that trisaccharides are better substrates than disaccharides and that one disaccharide, in which the terminal D-galactofuranose residue is replaced with an L-arabinofuranose moiety, is a weak substrate. Kinetic characterization of the enzyme using four of the oligosaccharide acceptors gave K(m) values ranging from 204 microM to 1.7 mM. Through the use of NMR spectroscopy and mass spectrometry, we demonstrated that this recombinant enzyme, like the wild-type protein, is bifunctional and can synthesize both beta-(1-->6) and beta-(1-->5)-linkages in an alternating fashion. Access to purified glfT is expected to facilitate the development of high-throughput assays for the identification of inhibitors of the enzyme, which are potential antituberculosis agents.


Subject(s)
Galactans/biosynthesis , Galactosyltransferases/biosynthesis , Galactosyltransferases/isolation & purification , Mycobacterium tuberculosis/enzymology , Bridged Bicyclo Compounds, Heterocyclic , Escherichia coli/metabolism , Galactosyltransferases/metabolism , Imidazoles , Kinetics , Mass Spectrometry , Nuclear Magnetic Resonance, Biomolecular , Substrate Specificity
6.
Carbohydr Res ; 341(10): 1702-7, 2006 Jul 24.
Article in English | MEDLINE | ID: mdl-16616902

ABSTRACT

The synthesis of an analog of the H-disaccharide antigen (2), in which the galactopyranosyl moiety bears an amino group at C-3 and the fucopyranosyl residue is deoxygenated at C-2, is reported. The key reaction in the preparation of 2 was the glycosylation of an appropriately protected n-octyl 3-azido-3-deoxy-galactopyranoside derivative with a 2,6-dideoxy thioglycoside promoted by 1-(phenylsulfinyl)piperidine and triflic anhydride. Disaccharide 2 is of interest in studies directed towards understanding the molecular basis of substrate recognition by the blood group A and B glycosyltransferases.


Subject(s)
Antigens, Bacterial/chemistry , Disaccharides/chemical synthesis , Carbohydrate Sequence
7.
Nat Struct Mol Biol ; 13(5): 460-1, 2006 May.
Article in English | MEDLINE | ID: mdl-16622409

ABSTRACT

Clostridium difficile TcdA is a large toxin that binds carbohydrates on intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3) binding in an extended conformation to TcdA. Residues forming key contacts with the trisaccharides are conserved in all seven putative binding sites in TcdA, suggesting a mode of multivalent binding that may be exploited for the rational design of novel therapeutics.


Subject(s)
Bacterial Toxins/chemistry , Bacterial Toxins/metabolism , Carbohydrate Metabolism , Carbohydrates/chemistry , Clostridioides difficile/chemistry , Clostridioides difficile/metabolism , Enterotoxins/chemistry , Enterotoxins/metabolism , Hydrogen Bonding , Models, Molecular , Protein Binding , Protein Structure, Tertiary
8.
J Org Chem ; 68(11): 4570-3, 2003 May 30.
Article in English | MEDLINE | ID: mdl-12762774

ABSTRACT

Catalyzed by a nitrile hydratase/amidase-containing microbial Rhodococcus sp. AJ270 whole-cell catalyst, a number of racemic trans-2,3-epoxy-3-arylpropanenitriles 1 underwent rapid and efficient hydrolysis under very mild conditions to afford 2R,3S-2-arylglycidamides 2 in excellent yield with enantiomeric excess higher than 99.5%. The overall enantioselectivity of the biotransformations originated from the combined effects of a dominantly high 2S-enantioselective amidase and low 2S-enantioselective nitrile hydratase involved in the cell. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects.


Subject(s)
Amides/chemical synthesis , Ethylene Oxide/analogs & derivatives , Ethylene Oxide/chemical synthesis , Hydro-Lyases/metabolism , Nitriles/chemistry , Rhodococcus/enzymology , Amides/analysis , Biotransformation , Catalysis , Ethylene Oxide/analysis , Kinetics , Molecular Structure , Stereoisomerism
9.
J Org Chem ; 67(18): 6542-5, 2002 Sep 06.
Article in English | MEDLINE | ID: mdl-12201779

ABSTRACT

Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of alpha-aryl- and alpha-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-alpha-amino acid amides 2 and L-(+)-alpha-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-alpha-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.


Subject(s)
Amides/chemical synthesis , Amidohydrolases/metabolism , Amino Acids/biosynthesis , Hydro-Lyases/metabolism , Rhodococcus/enzymology , Biotransformation , Catalysis , Hydrolysis , Nitriles/chemistry , Stereoisomerism , Substrate Specificity
10.
Se Pu ; 20(5): 407-10, 2002 Sep.
Article in Chinese | MEDLINE | ID: mdl-16358689

ABSTRACT

Enantiomers of nine arylglycine amides synthesized were successfully separated by capillary electrophoresis (CE) using highly sulfated beta-cyclodextrin (HS-beta-CD) as a chiral selector. Baseline enantioseparation of the analytes was obtained within 6 min at neutral pH but not the commonly used acidic condition. HS-beta-CD content, buffer type and concentration, and non-chiral additive were studied and optimized for high resolution and fast speed. A reproducible running buffer system composed of 15 g/L HS-beta-CD, 0 or 10% (volume fraction) methanol and 20 mmol/L 3-(N-morpholino) propane sulfonic acid at pH 6.5 was obtained. The D-enantiomer always migrated ahead of the L-enantiomer for all the 9 pairs of arylglycine amides. The migration order was found to be dependent on the structure of the solutes.


Subject(s)
Amides/chemistry , Electrophoresis, Capillary/instrumentation , Electrophoresis, Capillary/methods , Glycine/analogs & derivatives , beta-Cyclodextrins/chemistry , Stereoisomerism
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