Halogenase-Assisted\nAlkyne/Aryl Bromide Sonogashira\nCoupling for Ribosomally Synthesized Peptides

We describe the enzymatic bromination of ribosomally\nsynthesized\npeptides and develop protocols for Sonogashira coupling of peptidic\naryl bromides with a panel of alkynes. Using this workflow, entirely\nnew chemical handles are introduced onto ribosomal peptides, including\nbut not limited to terminal alkynes, which enable further diversification\nvia alkyne–azide click chemistry. Regiospecific enzymatic installation\nof the aryl bromide circumvents genetic code expansion and passivation\nof other reactive handles on the peptide chain, representing the applicability\nof biocatalysts in peptide modification chemistry.