Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis
- 10 May 2007
- journal article
- review article
- Published by Royal Society of Chemistry (RSC) in Natural Product Reports
- Vol. 24 (4), 735-749
- https://doi.org/10.1039/b613652b
Abstract
Covering: 2000 to 2006 Nonribosomal peptides and polyketides have attracted considerable attention in basic and applied research and have given rise to a multitude of therapeutic agents. The biological activity of many of these complex natural products, including for example the peptide antibiotics daptomycin and bacitracin or the polyketide anticancer agents epothilone and geldanamycin, specifically relies on the macrocyclization of linear acyl chains that form the backbone of these highly valuable molecules. The construction of the linear acyl precursors is accomplished by modular protein templates that follow comparable assembly line logic. As an enzymatic key step, macrocyclization is introduced after the consecutive condensation of amino acid or acyl-CoA building blocks by dedicated catalysts, and the mature product is released from the biosynthetic machinery. The diverse chain termination strategies of nonribosomal peptide and polyketide assembly lines, the structures and mechanisms of the versatile macrocyclization catalysts, and chemoenzymatic approaches for the development of new therapeutics are the focus of this review. Further, it is illustrated that macrocyclization is not restricted to secondary metabolites, but represents a commonly found structural motif of other biologically active proteins and peptides.Keywords
This publication has 94 references indexed in Scilit:
- Peptide Macrocyclization: The Reductase of the Nostocyclopeptide Synthetase Triggers the Self-Assembly of a Macrocyclic ImineJournal of the American Chemical Society, 2006
- Rational Design of Bacitracin A Derivatives by Incorporating Natural Product Derived HeterocyclesJournal of the American Chemical Society, 2006
- Assembly-Line Enzymology for Polyketide and Nonribosomal Peptide Antibiotics: Logic, Machinery, and MechanismsChemical Reviews, 2006
- The Thioesterase Domain of the Fengycin Biosynthesis Cluster: A Structural Base for the Macrocyclization of a Non-ribosomal LipopeptideJournal of Molecular Biology, 2006
- Combinatorial biosynthesis of reduced polyketidesNature Reviews Microbiology, 2005
- Bioactive Microbial MetabolitesThe Journal of Antibiotics, 2005
- Peptidyl Thiophenols as Substrates for Nonribosomal Peptide CyclasesAngewandte Chemie-International Edition, 2004
- Solution structure of PCP, a prototype for the peptidyl carrier domains of modular peptide synthetasesStructure, 2000
- High-resolution structure of a potent, cyclic proteinase inhibitor from sunflower seedsJournal of Molecular Biology, 1999
- Expression of an active adenylate‐forming domain of peptide synthetases corresponding to acyl‐CoA‐synthetasesFEBS Letters, 1995