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Updated: Feb 7, 2026

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
Published on: November 21, 2013
Structural, functional and evolutionary perspectives on effective re-engineering of non-ribosomal peptide synthetase
Alistair S Brown1, Mark J Calcott, Jeremy G Owen
1School of Biological Sciences, Victoria University of Wellington, New Zealand. david.ackerley@vuw.ac.nz.
Abstract:
Covering: up to May 2018 Non-ribosomal peptide synthetases (NRPSs) are mega-enzymes that form modular templates to assemble specific peptide products, independent of the ribosome. The autonomous nature of the modules in the template offers prospects for re-engineering NRPS enzymes to generate modified peptide products. Although this has clearly been a primary mechanism of natural product diversification throughout evolution, equivalent strategies have proven challenging to implement in the laboratory. In this review we examine key examples of successful and less-successful re-engineering of NRPS templates to generate novel peptides, with the aim of extracting practical guidelines to inform future efforts. We emphasise the importance of maintaining effective protein-protein interactions in recombinant NRPS templates, and identify strengths and limitations of diverse strategies for achieving different engineering outcomes.
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