Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains

Andrew D Gnann; Kenneth Marincin; Dominique P Frueh; Daniel P Dowling

doi:10.1016/j.cbpa.2022.102228

Dynamics and mechanistic interpretations of nonribosomal peptide synthetase cyclization domains

Curr Opin Chem Biol. 2023 Feb:72:102228. doi: 10.1016/j.cbpa.2022.102228. Epub 2022 Nov 16.

Authors

Andrew D Gnann¹, Kenneth Marincin², Dominique P Frueh², Daniel P Dowling³

Affiliations

¹ Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA.
² Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
³ Department of Chemistry, University of Massachusetts Boston, Boston, MA, 02125, USA. Electronic address: Daniel.Dowling@umb.edu.

PMID: 36402006
DOI: 10.1016/j.cbpa.2022.102228

Abstract

Ox-/thiazoline groups in nonribosomal peptides are formed by a variant of peptide-forming condensation domains called heterocyclization (Cy) domains and appear in a range of pharmaceutically important natural products and virulence factors. Recent cryo-EM, crystallographic, and NMR studies of Cy domains make it opportune to revisit outstanding questions regarding their molecular mechanisms. This review covers structural and dynamical findings about Cy domains that will inform future bioengineering efforts and our understanding of natural product synthesis.

Keywords: Allostery; Bioengineering; Cyclodehydration; Heterocycle; Pantetheine; Protein–protein interactions.

Publication types

Review

MeSH terms

Cyclization
Peptide Synthases* / metabolism
Peptides*
Protein Domains

Substances

non-ribosomal peptide synthase
Peptide Synthases
Peptides

Grants and funding

R15 GM123425/GM/NIGMS NIH HHS/United States