New structural data reveal the motion of carrier proteins in nonribosomal peptide synthesis

Tiia Kittila, Aurelio Mollo, Louise K. Charkoudian, Max J. Cryle

Research output: Contribution to journalReview ArticleResearchpeer-review

32 Citations (Scopus)


The nonribosomal peptide synthetases (NRPSs) are one of the most promising resources for the production of new bioactive molecules. The mechanism of NRPS catalysis is based around sequential catalytic domains: these are organized into modules, where each module selects, modifies, and incorporates an amino acid into the growing peptide. The intermediates formed during NRPS catalysis are delivered between enzyme centers by peptidyl carrier protein (PCP) domains, which makes PCP interactions and movements crucial to NRPS mechanism. PCP movement has been linked to the domain alternation cycle of adenylation (A) domains, and recent complete NRPS module structures provide support for this hypothesis. However, it appears as though the A domain alternation alone is insufficient to account for the complete NRPS catalytic cycle and that the loaded state of the PCP must also play a role in choreographing catalysis in these complex and fascinating molecular machines.
Original languageEnglish
Pages (from-to)9834-9840
Number of pages7
JournalAngewandte Chemie - International Edition
Issue number34
Publication statusPublished - 16 Aug 2016


  • biosynthesis
  • enzymes
  • nonribosomal peptide synthetases
  • peptidyl carrier protein
  • protein structures

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