Maturation of an Escherichia coli ribosomal peptide antibiotic by ATP-consuming N-P bond formation in microcin C7.

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.