Enzymatic Synthesis of a Polyketide/Nonribosomal Peptide\nHybrid Antibiotic, Salivabactin

Salivabactin\nis a newly identified polyketide/nonribosomal peptide\n(PK/NRP) from a human oral probiotic, possessing a unique chemical\nstructure and outstanding antibiotic activities. Although the biosynthetic\ngene cluster for salivabactin is known, the enzymatic logic that governs\nthe synthesis of salivabactin has not yet been fully studied. In this\nwork, we dissected the biosynthetic pathway for salivabactin using\nbiochemical analysis. We successfully reconstituted the enzymatic\nsynthesis of salivabactin in vitro, identified the minimal set of\nenzymes required for its biosynthesis, and revealed an unusual thioesterase\ndomain involved in terminal olefin formation.