Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023:2670:17-46.
doi: 10.1007/978-1-0716-3214-7_2.

Structural Studies of Modular Nonribosomal Peptide Synthetases

Ketan D Patel  1 , Syed Fardin Ahmed  1 , Monica R MacDonald  1 , Andrew M Gulick  2   3
Affiliations

Structural Studies of Modular Nonribosomal Peptide Synthetases

Ketan D Patel et al. Methods Mol Biol. 2023.

Abstract

The non-ribosomal peptide synthetases (NRPSs) are a family of modular enzymes involved in the production of peptide natural products. Not restricted by the constraints of ribosomal peptide and protein production, the NRPSs are able to incorporate unusual amino acids and other suitable building blocks into the final product. The NRPSs operate with an assembly line strategy in which peptide intermediates are covalently tethered to a peptidyl carrier protein and transported to different catalytic domains for the multiple steps in the biosynthesis. Often the carrier and catalytic domains are joined into a single large multidomain protein. This chapter serves to introduce the NRPS enzymes, using the nocardicin NRPS system as an example that highlights many common features to NRPS biochemistry. We then describe recent advances in the structural biology of NRPSs focusing on large multidomain structures that have been determined.

Keywords: Conformational changes; Modular enzymes; NRPS; Natural products; Non-ribosomal Peptide Synthetase; Protein–protein interactions; Secondary metabolites; Structural biology.

PubMed Disclaimer

References

    1. Newman DJ, Cragg GM (2020) Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J Nat Prod 83(3):770–803. https://doi.org/10.1021/acs.jnatprod.9b01285 - DOI - PubMed
    1. Süssmuth RD, Mainz A (2017) Nonribosomal peptide synthesis-principles and prospects. Angew Chem Int Ed Engl 56(14):3770–3821. https://doi.org/10.1002/anie.201609079 - DOI - PubMed
    1. Keating TA, Ehmann DE, Kohli RM, Marshall CG, Trauger JW, Walsh CT (2001) Chain termination steps in nonribosomal peptide synthetase assembly lines: directed acyl-S-enzyme breakdown in antibiotic and siderophore biosynthesis. Chembiochem 2(2):99–107 - DOI - PubMed
    1. Horsman ME, Hari TP, Boddy CN (2016) Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate? Nat Prod Rep 33(2):183–202. https://doi.org/10.1039/c4np00148f - DOI - PubMed
    1. Walsh CT (2016) Insights into the chemical logic and enzymatic machinery of NRPS assembly lines. Nat Prod Rep 33(2):127–135. https://doi.org/10.1039/c5np00035a - DOI - PubMed

Publication types

LinkOut - more resources