Issue 11, 2018

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

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

Article information

Article type
Review Article
Submitted
25 apr. 2018
First published
12 sep. 2018
This article is Open Access
Creative Commons BY license

Nat. Prod. Rep., 2018,35, 1120-1139

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

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements