Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin.
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.
Wieland Brown
Laura C
LC
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Acker
Michael G
MG
Clardy
Jon
J
Walsh
Christopher T
CT
Fischbach
Michael A
MA
D000595:Amino Acid Sequence; D001409:Bacillus cereus / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis* / Q000235:genetics / Q000494:pharmacology; D011499:Protein Processing, Post-Translational
D009842:Oligopeptides; D010455:Peptides; C012574:thiocillin