scholarly journals The biosynthetic implications of late-stage condensation domain selectivity during glycopeptide antibiotic biosynthesis

2019 ◽  
Vol 10 (1) ◽  
pp. 118-133 ◽  
Author(s):  
Melanie Schoppet ◽  
Madeleine Peschke ◽  
Anja Kirchberg ◽  
Vincent Wiebach ◽  
Roderich D. Süssmuth ◽  
...  
Keyword(s):  
Peptide Bond ◽  
Antibiotic Biosynthesis ◽  
Acid Activation ◽  
Adenylation Domain ◽  
Glycopeptide Antibiotic ◽  
Peptide Substrates ◽  
Amino Acid Activation ◽  
Linear Peptide ◽  
Peptide Formation ◽  
Condensation Domain

The condensation domain synthesising the last peptide bond in glycopeptide antibiotic biosynthesis has a preference for linear peptide substrates, with effective peptide formation linked to the rate of amino acid activation by the preceding adenylation domain.

scholarly journals Streptogramin B biosynthesis in Streptomyces pristinaespiralis and Streptomyces virginiae: molecular characterization of the last structural peptide synthetase gene.

1997 ◽  
Vol 41 (9) ◽  
pp. 1904-1909 ◽  
Author(s):  
V de Crécy-Lagard ◽  
W Saurin ◽  
D Thibaut ◽  
P Gil ◽  
L Naudin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Activation ◽  
Activation Domains ◽  
Amino Acid Activation ◽  
Streptomyces Virginiae ◽  
Streptomyces Pristinaespiralis ◽  
Degenerate Oligonucleotide ◽  
Peptide Synthetase ◽  
Different Origins

Streptomyces pristinaespiralis and S. virginiae both produce closely related hexadepsipeptide antibiotics of the streptogramin B family. Pristinamycins I and virginiamycins S differ only in the fifth incorporated precursor, di(mono)methylated amine and phenylalanine, respectively. By using degenerate oligonucleotide probes derived from internal sequences of the purified S. pristinaespiralis SnbD and SnbE proteins, the genes from two streptogramin B producers, S. pristinaespiralis and S. virginiae, encoding the peptide synthetase involved in the activation and incorporation of the last four precursors (proline, 4-dimethylparaaminophenylalanine [for pristinamycin I(A)] or phenylalanine [for virginiamycin S], pipecolic acid, and phenylglycine) were cloned. Analysis of the sequence revealed that SnbD and SnbE are encoded by a unique snbDE gene. SnbDE (4,849 amino acids [aa]) contains four amino acid activation domains, four condensation domains, an N-methylation domain, and a C-terminal thioesterase domain. Comparison of the sequences of 55 amino acid-activating modules from different origins confirmed that these sequences contain enough information for the performance of legitimate predictions of their substrate specificity. Partial sequencing (1,993 aa) of the SnbDE protein of S. virginiae allowed comparison of the proline and aromatic acid activation domains of the two species and the identification of coupled frameshift mutations.

scholarly journals The Mechanism of Amino Acid Activation: the Work of Mahlon Hoagland

2009 ◽  
Vol 284 (25) ◽  
pp. e7-e8
Author(s):  
Nicole Kresge ◽  
Robert D. Simoni ◽  
Robert L. Hill
Keyword(s):  
Amino Acid ◽  
Acid Activation ◽  
Amino Acid Activation

scholarly journals Halogenation of glycopeptide antibiotics occurs at the amino acid level during non-ribosomal peptide synthesis

2017 ◽  
Vol 8 (9) ◽  
pp. 5992-6004 ◽  
Author(s):  
Tiia Kittilä ◽  
Claudia Kittel ◽  
Julien Tailhades ◽  
Diane Butz ◽  
Melanie Schoppet ◽  
...  
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Acid Level ◽  
Amino Acid Level ◽  
Antibiotic Biosynthesis ◽  
Carrier Protein ◽  
Glycopeptide Antibiotics ◽  
Glycopeptide Antibiotic ◽  
Protein Substrates

Halogenase enzymes involved in glycopeptide antibiotic biosynthesis accept aminoacyl-carrier protein substrates.

scholarly journals The Contribution of Syringopeptin and Syringomycin to Virulence of Pseudomonas syringae pv. syringae strain B301D on the Basis of sypA and syrB1 Biosynthesis Mutant Analysis

2001 ◽  
Vol 14 (3) ◽  
pp. 336-348 ◽  
Author(s):  
Brenda K. Scholz-Schroeder ◽  
Michael L. Hutchison ◽  
Ingeborg Grgurina ◽  
Dennis C. Gross
Keyword(s):  
Pseudomonas Syringae ◽  
High Performance ◽  
Sweet Cherry ◽  
Peptide Structure ◽  
Acid Activation ◽  
Virulence Determinants ◽  
Amino Acid Activation ◽  
Peptide Synthetases ◽  
Peptide Synthetase ◽  
Peptide Biosynthesis

Sequencing of an approximately 3.9-kb fragment downstream of the syrD gene of Pseudomonas syringae pv. syringae strain B301D revealed that this region, designated sypA, codes for a peptide synthetase, a multifunctional enzyme involved in the thiotemplate mechanism of peptide biosynthesis. The translated protein sequence encompasses a complete amino acid activation module containing the conserved domains characteristic of peptide synthetases. Analysis of the substrate specificity region of this module indicates that it incorporates 2,3-dehydroaminobutyric acid into the syringopeptin peptide structure. Bioassay and high performance liquid chromatography data confirmed that disruption of the sypA gene in strain B301D resulted in the loss of syringopeptin production. The contribution of syringopeptin and syringomycin to the virulence of P. syringae pv. syringae strain B301D was examined in immature sweet cherry with sypA and syrB1 synthetase mutants defective in the production of the two toxins, respectively. Syringopeptin (sypA) and syringomycin (syrB1) mutants were reduced in virulence 59 and 26%, respectively, compared with the parental strain in cherry, whereas the syringopeptin-syringomycin double mutant was reduced 76% in virulence. These data demonstrate that syringopeptin and syringomycin are major virulence determinants of P. syringae pv. syringae.

Amino-Acid Activation in Tissues of Early Embryos

Nature ◽  
1961 ◽  
Vol 191 (4792) ◽  
pp. 1006-1007 ◽  
Author(s):  
ELIZABETH M. DEUCHAR
Keyword(s):  
Amino Acid ◽  
Acid Activation ◽  
Amino Acid Activation ◽  
Early Embryos

scholarly journals Use of a spectrophotometric assay to evaluate amino acid activation and tRNA charging

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Japheth Mobisa ◽  
Kyra Samuel ◽  
Idiuso Okeke ◽  
Jacquelyn Castaneda ◽  
Thanh Trinh ◽  
...  
Keyword(s):  
Amino Acid ◽  
Spectrophotometric Assay ◽  
Acid Activation ◽  
Amino Acid Activation

scholarly journals Thioesters Provide a Robust Path to Prebiotic Peptides

2021 ◽  
Author(s):  
Moran Frenkel-Pinter ◽  
Marcos Bouza ◽  
Facundo M. Fernández ◽  
Luke J. Leman ◽  
Loren Dean Williams ◽  
...  
Keyword(s):  
Building Blocks ◽  
Peptide Bond ◽  
Side Reactions ◽  
Peptide Bond Formation ◽  
One Pot ◽  
Complex Molecules ◽  
Peptide Formation ◽  
Wide Range ◽  
Amide Exchange ◽  
Prebiotic Earth

The condensation of building blocks into oligomers and polymers was an early and important stage in the origins of life. High activation energies, unfavorable thermodynamics and side reactions are bottlenecks for abiotic formation of peptides. Thioesters are hypothesized to have played key roles in prebiotic chemistry on early Earth, serving as energy storing molecules, as synthetic intermediates, and as catalysts in the formation of more complex molecules, including polypeptides. However, all abiotic reactions reported thus far for peptide formation via thioester intermediates have relied on activated building blocks or condensing agents, which are of questionable prebiotic relevance. We report robust, plausible prebiotic reactions of mercaptoacids with amino acids that result in the formation of peptides and thiodepsipeptides, which contain both peptide and thioester bonds. Peptide bond formation proceeds by the condensation of mercaptoacids to form thioesters followed by thioester-amide exchange. Mercaptoacids catalyze thiodepsipeptides and peptide formation under a wide range of pH conditions and at mild temperatures. Our results offer the most robust one-pot pathway for peptide formation ever reported. These results support the hypothesis that thiodepsipeptides formed robustly on prebiotic Earth and were possible contributors to early chemical evolution.

scholarly journals A systematic series of synthetic chromophoric substrates for aspartic proteinases

1986 ◽  
Vol 237 (3) ◽  
pp. 899-906 ◽  
Author(s):  
B M Dunn ◽  
M Jimenez ◽  
B F Parten ◽  
M J Valler ◽  
C E Rolph ◽  
...  
Keyword(s):  
Structure Function ◽  
Peptide Bond ◽  
Water Soluble ◽  
Animal Origin ◽  
Aspartic Proteinases ◽  
Peptide Substrates ◽  
Representative Selection ◽  
Micro Organisms ◽  
Hydrolysis Of ◽  
Selection Of

The hydrolysis of the chromogenic peptide Pro-Thr-Glu-Phe-Phe(4-NO2)-Arg-Leu at the Phe-Phe(4-NO2) bond by nine aspartic proteinases of animal origin and seven enzymes from micro-organisms is described [Phe(4-NO2) is p-nitro-L-phenylalanine]. A further series of six peptides was synthesized in which the residue in the P3 position was systematically varied from hydrophobic to hydrophilic. The Phe-Phe(4-NO2) bond was established as the only peptide bond cleaved, and kinetic constants were obtained for the hydrolysis of these peptide substrates by a representative selection of aspartic proteinases of animal and microbial origin. The value of these water-soluble substrates for structure-function investigations is discussed.

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