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The biosynthesis of the lantibiotics epidermin, gallidermin, Pep5 and epilancin K7

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Abstract

Lantibiotics are antibiotic peptides that contain the rare thioether amino acids lanthionine and/or methyllanthionine. Epidermin, Pep5 and epilancin K7 are produced by Staphylococcus epidermidis whereas gallidermin (6L-epidermin) was isolated from the closely related species Staphylococcus gallinarum. The biosynthesis of all four lantibiotics proceeds from structural genes which code for prepeptides that are enzymatically modified to give the mature peptides. The genes involved in biosynthesis, processing, export etc. are found in gene clusters adjacent to the structural genes and code for transporters, immunity functions, regulatory proteins and the modification enzymes LanB, LanC and LanD, which catalyze the biosynthesis of the rare amino acids. LanB and LanC are responsible for the dehydration of the serine and threonine residues to give dehydroalanine and dehydrobutyrine and subsequent addition of cysteine SH-groups to the dehydro amino acids which results in the thioether rings. EpiD, the only LanD enzyme known so far, catalyzes the oxidative decarboxylation of the C-terminal cysteine of epidermin which gives the C-terminal S-aminovinylcysteine after addition of a dehydroalanine residue.

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Abbreviations

Dha:

2,3-didehydroalanine

Dhb:

2,3-didehydrobutyrine

Lan:

lanthionine

Melan:

methyllanthionine

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Authors and Affiliations

  1. Institut für Medizinische Mikrobiologie der Universität Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany

    Gabriele Bierbaum & Hans-Georg Sahl

  2. Mikrobielle Genetik, Universität Tübingen, Waldhäuser Str. 70/8, D-72076, Tübingen, Germany

    Friedrich Götz, Andreas Peschel & Thomas Kupke

  3. Laboratory of Biophysical Chemistry, Universiteit Nijmegen, Toernooiveld, NL-6526 ED, Nijmegen, the Netherlands

    Mart van de Kamp

Authors
  1. Gabriele Bierbaum
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  2. Friedrich Götz
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  3. Andreas Peschel
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  4. Thomas Kupke
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  5. Mart van de Kamp
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  6. Hans-Georg Sahl
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Bierbaum, G., Götz, F., Peschel, A. et al. The biosynthesis of the lantibiotics epidermin, gallidermin, Pep5 and epilancin K7. Antonie van Leeuwenhoek 69, 119–127 (1996). https://doi.org/10.1007/BF00399417

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