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- Title
Stereochemistry and Conformation of Skyllamycin, a Non-Ribosomally Synthesized Peptide from Streptomyces sp. Acta 2897.
- Authors
Schubert, Vivien; Di Meo, Florent; Saaidi, Pierre ‐ Loïc; Bartoschek, Stefan; Fiedler, Hans ‐ Peter; Trouillas, Patrick; Süssmuth, Roderich D.
- Abstract
Skyllamycin is a non-ribosomally synthesized cyclic depsipeptide from Streptomyces sp. Acta 2897 that inhibits PDGF-signaling. The peptide scaffold contains an N-terminal cinnamoyl moiety, a β-methylation of aspartic acid, three β-hydroxylated amino acids and one rarely occurring α-hydroxy glycine. With the exception of α-hydroxy glycine, the stereochemistry of the amino acids was assigned by comparison to synthetic reference amino acids applying chiral GC-MS and Marfey-HPLC analysis. The stereochemistry of α-hydroxy glycine, which is unstable under basic and acidic conditions, was determined by conformational analysis, employing a combination of data from NOESY-NMR spectroscopy, simulated annealing and free MD simulations. The simulation procedures were applied for both R- and S-configured α-hydroxy glycine of the skyllamycin structure and compared to the NOESY data. Both methods, simulated annealing and free MD simulations independently support S-configured α-hydroxy glycine thus enabling the assignment of all stereocenters in the structure of skyllamycin and devising the role of two-component flavin dependent monooxygenase (Sky39) as S-selective.
- Subjects
PEPTIDE analysis; STEREOCHEMISTRY; CONFORMATIONAL analysis; PEPTIDE antibiotics; NUCLEAR magnetic resonance spectroscopy; HIGH performance liquid chromatography
- Publication
Chemistry - A European Journal, 2014, Vol 20, Issue 17, p4948
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201304562