title: Maturation of an Escherichia coli ribosomal peptide antibiotic by ATP-consuming N-P bond formation in microcin C7.
abstract: Synthetic phosphoramidate analogues of nucleosides have been used as enzyme inhibitors for decades and have therapeutic applications in the treatments of HIV and cancer, but little is known about how N-P bonds are fashioned in nature. The heptapeptide MccA undergoes post-translational processing in producer strains of Escherichia coli to afford microcin C7 (MccC7), a "Trojan horse" antibiotic that contains a phosphoramidate linkage to adenosine monophosphate at its C-terminus. We show that the enzyme MccB, encoded by the MccC7 gene cluster, is responsible for formation of the N-P bond in MccC7. This modification requires the consumption of two ATP molecules per MccA peptide and formation and breakdown of a peptidyl-succinimide intermediate.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Roush
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Nolan
authors.forename: Frank
authors.initials: F
authors.lastname: Löhr
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
mesh_terms: D000249:Adenosine Monophosphate / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism*; D000577:Amides / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D001430:Bacteriocins / Q000096:biosynthesis* / Q000737:chemistry; D002384:Catalysis; D003001:Cloning, Molecular; D004789:Enzyme Activation; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008968:Molecular Conformation; D009842:Oligopeptides / Q000096:biosynthesis* / Q000737:chemistry; D010756:Phosphoric Acids / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D009842:Oligopeptides; D010756:Phosphoric Acids; C020411:microcin; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; C011067:phosphoramidic acid