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Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2549-53. doi: 10.1073/pnas.0900008106. Epub 2009 Feb 5.

Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin.

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  • 1Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.


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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