Polyketide and Nonribosomal Peptide Antibiotics: Modularity and Versatility

@article{Walsh2004PolyketideAN,
  title={Polyketide and Nonribosomal Peptide Antibiotics: Modularity and Versatility},
  author={Christopher T Walsh},
  journal={Science},
  year={2004},
  volume={303},
  pages={1805 - 1810}
}
  • C. Walsh
  • Published 19 March 2004
  • Biology, Medicine
  • Science
Polyketide (PK) and nonribosomal peptides (NRP), constructed on multimodular enzymatic assembly lines, often attain the conformations that establish biological activity by cyclization constraints introduced by tailoring enzymes. The dedicated tailoring enzymes are encoded by genes clustered with the assembly line genes for coordinated regulation. NRP heterocyclizations to thiazoles and oxazoles can occur on the elongating framework of acyl-S enzyme intermediates, whereas tandem cyclic PK… 
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  • C. Walsh
  • Chemistry, Medicine
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  • 2008
TLDR
Analysis of the types of protein domains that carry out chain initiation, elongation, tailoring, and termination steps gives insight into how NRP and PK biosynthetic assembly lines can be redirected to make novel molecules.
Structural insights into nonribosomal peptide enzymatic assembly lines.
TLDR
Recent breakthrough achievements in both X-ray and NMR spectroscopic studies are reviewed that illuminate the architecture of NRPS PCP domains, PCP-containing didomain-fragments and of a full termination module (C-A-PCP-TE).
Rational Manipulation of Carrier‐Domain Geometry in Nonribosomal Peptide Synthetases
  • Ye Liu, S. Bruner
  • Chemistry, Medicine
    Chembiochem : a European journal of chemical biology
  • 2007
TLDR
An approach to manipulate the carrier-domain geometry of NRPS assemblies through the application of isosteric nonhydrolyzable analogues of phosphopantetheinyl thioester mimics is reported, which will be useful in elucidating the complex structure and mechanism of synthetases.
The Assembly Line Enzymology of Polyketide Biosynthesis.
TLDR
An introductory primer to modular polyketide synthase structure and function is provided, and recent advances in the characterization and exploitation of these systems are highlighted.
Chapter 2 The Assembly Line Enzymology of Polyketide Biosynthesis
Polyketides are a structurally and functionally diverse family of bioactive natural products that have found widespread application as pharmaceuticals, agrochemicals, and veterinary medicines. In
Dynamic thiolation–thioesterase structure of a non-ribosomal peptide synthetase
TLDR
The T–TE interaction described here provides a model for NRPS, PKS and FAS function in general as T– TE-like di-domains typically catalyse the last step in numerous assembly-line chain-termination machineries.
Nonribosomal Peptide Synthetases
TLDR
The chemistry and structure of nonribosomal peptide (NRP) biosynthetic machinery responsible for the construction of peptide-based natural products including the clinically important vancomycin and penicillin antibiotics are described.
The biosynthetic logic of polyketide diversity.
TLDR
This review highlights recently unveiled biosynthetic mechanisms to generate highly diverse and complex molecules that lead to the large structural diversity of polyketides.
Nonribosomal Peptide and Polyketide Biosynthesis
  • B. Evans
  • Biology
    Methods in Molecular Biology
  • 2016
TLDR
The structures of NRPS proteins are described and the strategies that are being used to assist structural studies of these dynamic proteins, including careful consideration of domain boundaries for generation of truncated proteins and the use of mechanism-based inhibitors that trap interactions between the catalytic and carrier protein domains.
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