Feglymycin

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Feglymycin
Feglymycin
3D structure of the feglymycin dimer as a rod model, from the side and front, according to PDB  1W7R

Existing structural data : 1W7R , 1W7Q

Mass / length primary structure 13 aa; 1,900.882 g / mol, C 95 H 97 N 13 O 30
Identifier
External IDs
Occurrence
Parent taxon Streptomyces

Structural formula

In feglymycin is an antiviral and an antibiotic . It could be obtained from cultures of Streptomyces sp. By solid phase extraction , gel permeation chromatography and reversed phase chromatography . DSM 11171 can be obtained.

properties

Feglymycin is a protein made up of 13 amino acids , whereby the non-proteinogenic amino acids 4-hydroxyphenylglycine (four pieces) and 3,5-dihydroxyphenylglycine (five pieces) are mostly arranged alternately. It forms asymmetric dimers with an antiparallel, double-stranded double-β 9.0 helix.

In vitro , feglymycin showed activity against the human immunodeficiency virus and against Staphylococcus aureus . The antiviral effect is achieved by inhibiting the binding of gp120 to CD4 . The antibiotic effect arises from the inhibition of the enzymes MurA and MurC of the bacterial peptidoglycan biosynthesis. An aspartate at position 13 is essential here.

The biosynthesis of feglymycin is carried out by nonribosomal peptide synthesis involved in the 19 proteins ( FeGa-FEG ).

The total synthesis of feglymycin was published in 2009, and another in 2016.

Individual evidence

  1. ↑ Bunkóczi, Gábor: Structure determination of peptides with antimicrobial action (PDF; 14.4 MB).
  2. ↑ a b G. ferir, A. Chicken, KO François, B. Hoorelbeke, D. Huskens, F. Dettner, RD Siissmuth, D. Schols: feglymycin, a unique natural bacterial antibiotic peptides Inhibits HIV entry by targeting the viral envelope protein gp120. In: Virology. Volume 433, Number 2, November 2012, pp. 308-319, doi : 10.1016 / j.virol.2012.08.007 , PMID 22959895 .
  3. ^ S. Rausch, A. Hänchen, A. Denisiuk, M. Löhken, T. Schneider, RD Süssmuth: Feglymycin is an inhibitor of the enzymes MurA and MurC of the peptidoglycan biosynthesis pathway. In: Chembiochem: a European journal of chemical biology. Volume 12, Number 8, May 2011, pp. 1171-1173, doi : 10.1002 / cbic.201100120 , PMID 21538763 .
  4. ↑ a b A. Hänchen, S. Rausch, B. Landmann, L. Toti, A. Nusser, RD Süssmuth: Alanine scan of the peptide antibiotic feglymycin: assessment of amino acid side chains contributing to antimicrobial activity. In: Chembiochem: a European journal of chemical biology. Volume 14, number 5, March 2013, pp. 625-632, doi : 10.1002 / cbic.201300032 , PMID 23447362 .
  5. ↑ M. Gonsior, A. Mühlenweg, M. Tietzmann, S. Rausch, A. Poch, RD Süssmuth: Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism. In: Chembiochem: a European journal of chemical biology. Volume 16, number 18, December 2015, pp. 2610-2614, doi : 10.1002 / cbic.201500432 , PMID 26515424 .
  6. ↑ Frank Dettner, Anne Hänchen, Dominique Schols, Luigi Toti, Antje Nußer, Roderich D. Süssmuth: Total synthesis of the antiviral peptide antibiotic feglymycin. In: Angewandte Chemie. 121, 2009, p. 1888, doi : 10.1002 / anie.200804130 .
  7. ↑ S. Fuse, Y. Mifune, H. Nakamura, H. Tanaka: Total synthesis of feglymycin based on a linear / convergent hybrid approach using micro-flow amide bond formation. In: Nature Communications . Volume 7, November 2016, p. 13491, doi : 10.1038 / ncomms13491 , PMID 27892469 , PMC 5133696 (free full text).