Substituent Effects on the Phenol Coupling Reaction Catalyzed by the Vancomycin Biosynthetic P450 Enzyme OxyB

Oxidative phenol coupling reactions are required to establish the cross-linked heptapeptide backbone of vancomycin. The first cross-linking reaction, catalyzed by the P450 enzyme OxyB, is dramatically slower when a chlorine substituent is present in the hexapeptide-S-PCP substrate and is abolished when chlorine is introduced into a potential heptapeptide-S-PCP substrate.