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Genetic manipulation of non-ribosomal peptide synthetases to generate novel bioactive peptide products

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Abstract

Non-ribosomal peptide synthetases (NRPS) are large modular enzymes that govern the synthesis of numerous biotechnologically relevant products. Their mode of action is frequently compared to an assembly line, in which each module acts in a semi-autonomous but coordinated manner to add a specific monomer to a growing peptide chain, unfettered by ribosomal constraints. The modular nature of these systems offers tantalising prospects for synthetic biology, wherein the assembly line is re-engineered at a genetic level to generate a specific or combinatorial modified product. However, despite some success stories, a “one size fits all” approach to NRPS synthetic biology remains elusive. This review examines both rational and random mutagenesis strategies that have been employed to modify NRPS function, in an attempt to highlight key points that should be considered when seeking to re-engineer an NRPS biosynthetic template.

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Acknowledgments

The authors would like to acknowledge financial support from the Royal Society of New Zealand Marsden Fund [contract number VUW0901].

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Authors and Affiliations

  1. School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand

    Mark J. Calcott & David F. Ackerley

  2. Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand

    David F. Ackerley

  3. Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New Zealand

    David F. Ackerley

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  1. Mark J. Calcott
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  2. David F. Ackerley
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Correspondence to David F. Ackerley.

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Calcott, M.J., Ackerley, D.F. Genetic manipulation of non-ribosomal peptide synthetases to generate novel bioactive peptide products. Biotechnol Lett 36, 2407–2416 (2014). https://doi.org/10.1007/s10529-014-1642-y

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  • DOI: https://doi.org/10.1007/s10529-014-1642-y

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