Protein–Protein Interactions in Multienzyme Megasynthetases

@article{Weissman2008ProteinProteinII,
  title={Protein–Protein Interactions in Multienzyme Megasynthetases},
  author={Kira J. Weissman and Rolf M{\"u}ller},
  journal={ChemBioChem},
  year={2008},
  volume={9}
}
The multienzyme polyketide synthases (PKSs), nonribosomal polypeptide synthetases (NRPSs), and their hybrids are responsible for the construction in bacteria of numerous natural products of clinical value. These systems generate high structural complexity by using a simple biosynthetic logic—that of the assembly line. Each of the individual steps in building the metabolites is designated to an independently folded domain within gigantic polypeptides. The domains are clustered into functional… 
Insights into Multienzyme Docking in Hybrid PKS–NRPS Megasynthetases Revealed by Heterologous Expression and Genetic Engineering
TLDR
Reflecting the shared biosynthetic logic of modular PKS and NRPS, numerous systems have been discovered to date in which both types of multienzymes collaborate to form hybrid polyketide–polypeptide natural products.
Uncovering the structures of modular polyketide synthases.
TLDR
This review aims to compare the cryo-EM structures and SAXS-derived structural models, and to interpret them in the context of previously obtained data and existing architectural proposals, to discuss the consequences for genetic engineering of the systems.
Protein-protein interactions in "cis-AT" polyketide synthases.
TLDR
The structural and biochemical results that shed light on the protein-protein interactions critical to catalysis by PKS systems with an embedded acyltransferase are reviewed.
Docking domain-mediated subunit interactions in natural product megasynth(et)ases
TLDR
This review details all structurally characterised examples of NRPS and PKS DDs to date and summarises efforts to utilise DDs for the engineering of biosynthetic pathways.
Mechanism of Subunit Interaction at Ketosynthase-Dehydratase Junctions in transAT Polyketide Synthases
TLDR
A fundamentally different mechanism for subunit assembly in trans-AT modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains is reported, which involves direct interaction of a largely unstructured docking domain (DD) at the C-terminus of the KS with the surface of the downstream DH.
Structural basis for chain release from the enacyloxin polyketide synthase
TLDR
Communication between two non-ribosomal peptide synthetase subunits responsible for chain release from the enacyloxin polyketide synthase, which assembles an antibiotic with promising activity against Acinetobacter baumannii, is mediated by an intrinsically disordered short linear motif and a β-hairpin docking domain.
Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines.
MOTIVATION Polyketide synthases are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many
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TLDR
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TLDR
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