title: Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin.
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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Wieland Brown
authors.forename: Michael G
authors.initials: MG
authors.lastname: Acker
authors.forename: Jon
authors.initials: J
authors.lastname: Clardy
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischbach
mesh_terms: 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
chemical_list: D009842:Oligopeptides; D010455:Peptides; C012574:thiocillin