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Updated: Jun 25, 2026

Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin
Laura C Wieland Brown1, Michael G Acker, Jon Clardy
1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Abstract:
The thiazolylpeptides are a family of >50 bactericidal antibiotics that block the initial steps of bacterial protein synthesis. Here, we report a biosynthetic gene cluster for thiocillin and establish that it, and by extension the whole class, is ribosomally synthesized. Remarkably, the C-terminal 14 residues of a 52-residue peptide precursor undergo 13 posttranslational modifications to give rise to thiocillin, making this antibiotic the most heavily posttranslationally-modified peptide known to date.
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