title: Diversity of nature's assembly lines - recent discoveries in non-ribosomal peptide synthesis.
abstract: The biosynthesis of complex natural products by non-ribosomal peptide synthetases (NRPSs) and the related polyketide synthases (PKSs) represents a major source of important bioactive compounds. These large, multi-domain machineries are able to produce a fascinating range of molecules due to the nature of their modular architectures, which allows natural products to be assembled and tailored in a modular, step-wise fashion. In recent years there has been significant progress in characterising the important domains and underlying mechanisms of non-ribosomal peptide synthesis. More significantly, several studies have uncovered important examples of novel activity in many NRPS domains. These discoveries not only greatly increase the structural diversity of the possible products of NRPS machineries but - possibly more importantly - they improve our understanding of what is a highly important, yet complex, biosynthetic apparatus. In this review, several recent examples of novel NRPS function will be introduced, which highlight the range of previously uncharacterised activities that have now been detected in the biosynthesis of important natural products by these mega-enzyme synthetases.
authors.affiliation: EMBL Australia, Monash University, Clayton, Victoria 3800, Australia and The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia. max.cryle@monash.edu.
authors.forename: Jennifer A E
authors.identifier: http://orcid.org/0000-0002-4711-0501
authors.initials: JA
authors.lastname: Payne
authors.affiliation: EMBL Australia, Monash University, Clayton, Victoria 3800, Australia and The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia. max.cryle@monash.edu.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schoppet
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Mathias Henning
authors.initials: MH
authors.lastname: Hansen
authors.affiliation: EMBL Australia, Monash University, Clayton, Victoria 3800, Australia and The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology and ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia. max.cryle@monash.edu.
authors.forename: Max J
authors.identifier: http://orcid.org/0000-0002-9739-6157
authors.initials: MJ
authors.lastname: Cryle
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry; D010452:Peptide Biosynthesis; D010453:Peptide Synthases / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism; D014176:Protein Biosynthesis; D015202:Protein Engineering; D054730:Protein Interaction Domains and Motifs
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D048630:Polyketide Synthases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase