Tyroci dines

In non-i ibosomal biosynthesis of peptide antibiotics by multimodular synthetases, amino acid monomers ai e activated by the adenylation domains of the synthetase and loaded onto the adjacent canier protein domains as thioesters, then the formation of peptide bonds and translocation of the growing chain are effected by the synthetase s condensation domains. Whether the condensation domains have any editing function has been unknown. Synthesis of aminoacyl-CoA molecules and direct enzymatic transfer of aminoacyl-phospho-pantetheine to the caiiier domains allow the adenylation domain editing function to be bypassed. This method was used to demonstrate that the first condensation domain of tyroci-dine synthetase shows low selectivity at the donor residue (D-phenyManine) and higher selectivity at the acceptor residue (L-proline) in the formation of the chain-initiating D-Phe-L-Pro dipeptidyl-enzyme intermediate. 

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