Aminoacyl-CoAs as Probes of Condensation Domain Selectivity in Nonribosomal Peptide Synthesis

+ See all authors and affiliations

Science  16 Apr 1999:
Vol. 284, Issue 5413, pp. 486-489
DOI: 10.1126/science.284.5413.486

You are currently viewing the abstract.

View Full Text


In nonribosomal biosynthesis of peptide antibiotics by multimodular synthetases, amino acid monomers are activated by the adenylation domains of the synthetase and loaded onto the adjacent carrier 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–coenzyme A (CoA) molecules and direct enzymatic transfer of aminoacyl-phosphopantetheine to the carrier domains allow the adenylation domain editing function to be bypassed. This method was used to demonstrate that the first condensation domain of tyrocidine synthetase shows low selectivity at the donor residue (d-phenylalanine) and higher selectivity at the acceptor residue (l-proline) in the formation of the chain-initiating d-Phe-l-Pro dipeptidyl-enzyme intermediate.

  • * These authors contributed equally to this work.

View Full Text