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Issue 11, 2018
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The many faces and important roles of protein–protein interactions during non-ribosomal peptide synthesis

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Abstract

Covering: up to July 2018

Non-ribosomal peptide synthetase (NRPS) machineries are complex, multi-domain proteins that are responsible for the biosynthesis of many important, peptide-derived compounds. By decoupling peptide synthesis from the ribosome, NRPS assembly lines are able to access a significant pool of amino acid monomers for peptide synthesis. This is combined with a modular protein architecture that allows for great variation in stereochemistry, peptide length, cyclisation state and further modifications. The architecture of NRPS assembly lines relies upon a repetitive set of catalytic domains, which are organised into modules responsible for amino acid incorporation. Central to NRPS-mediated biosynthesis is the carrier protein (CP) domain, to which all intermediates following initial monomer activation are bound during peptide synthesis up until the final handover to the thioesterase domain that cleaves the mature peptide from the NRPS. This mechanism makes understanding the protein–protein interactions that occur between different NRPS domains during peptide biosynthesis of crucial importance to understanding overall NRPS function. This endeavour is also highly challenging due to the inherent flexibility and dynamics of NRPS systems. In this review, we present the current state of understanding of the protein–protein interactions that govern NRPS-mediated biosynthesis, with a focus on insights gained from structural studies relating to CP domain interactions within these impressive peptide assembly lines.

Graphical abstract: The many faces and important roles of protein–protein interactions during non-ribosomal peptide synthesis

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Article information


Submitted
25 apr. 2018
First published
12 sep. 2018

This article is Open Access

Nat. Prod. Rep., 2018,35, 1120-1139
Article type
Review Article

The many faces and important roles of protein–protein interactions during non-ribosomal peptide synthesis

T. Izoré and M. J. Cryle, Nat. Prod. Rep., 2018, 35, 1120
DOI: 10.1039/C8NP00038G

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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