Editorial: Biosynthetic assembly lines themed issue
A structural model for multimodular NRPS assembly lines
This viewpoint article focuses on the structures of the dissected catalytic domains of non-ribosomal peptide synthetases and how these structural details of the NRPS machinery, integrated in a didomain and an elongation module were used to generate a model for a multimodular NRPS assembly line.
Insights into the chemical logic and enzymatic machinery of NRPS assembly lines
Appreciation that some cyclic peptide antibiotics such as gramicidin S and tyrocidine were nonribosomally synthesized has been known for 50 years.
New tools for reconstruction and heterologous expression of natural product biosynthetic gene clusters
Here we describe recent advances in DNA assembly and host engineering and highlight their applications in natural product discovery and engineering.
Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines
In this Highlight, we focus on some newly characterized cyclization reactions that occur on and off the PKS and NRPS assembly lines, for the purpose of elucidating template effects in various manners.
Stereocontrol within polyketide assembly lines
The current structural and functional data on modular polyketide synthase enzymes and their relatives has enabled the construction of physical models for how KS, KR, DH, and ER set stereocenters.
Recent advances in the biosynthesis of unusual polyketide synthase substrates
Polyketides comprise a diverse class of natural products, with many important biological and pharmacological activities. Substrates functioning as starter units and extender units during their assembly significantly contribute to the chemical complexity exhibited by this class of natural products. This highlight provides an overview of the recent advances in understanding the diversity of these polyketide synthase (PKS) building blocks.
Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis
This highlight focuses on one of Nature's key strategies to doubly modify an amino acid during nonribosomal peptide biosynthesis by using a single enzyme, an interrupted adenylation domain.
Unique marine derived cyanobacterial biosynthetic genes for chemical diversity
Cyanobacteria are a prolific source of structurally unique and biologically active natural products that derive from intriguing biochemical pathways.
Review Article
Recent advances in engineering nonribosomal peptide assembly lines
This reviews summarises progress towards the engineering of nonribosomal peptide synthetases (NRPS) from the expression of heterologous tailoring enzymes to direct modifications of the assembly lines to produce analogues. New techniques/tools for introducing changes are also examined.
Biosynthesis of polyketides by trans-AT polyketide synthases
This review discusses the biosynthesis of natural products that are generated by trans-AT polyketide synthases, a family of catalytically versatile enzymes that represents one of the major group of proteins involved in the production of bioactive polyketides.
Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology
This reviews covers on-going efforts at engineering the gigantic modular polyketide synthases (PKSs), highlighting both notable successes and failures.
Polyketide synthase and non-ribosomal peptide synthetase thioesterase selectivity: logic gate or a victim of fate?
Thioesterases (TEs) are product offloading enzymes from FAS, PKS, and NRPS complexes. We review the diversity, structure, and mechanism of PKS and NRPS TEs and analyze TE loading and release steps as possible logic gates with a view to predicting TE function in new pathways.
Uncovering the structures of modular polyketide synthases
This review covers a breakthrough in the structural biology of the gigantic modular polyketide synthases (PKS): the structural characterization of intact modules by single-particle cryo-electron microscopy and small-angle X-ray scattering.
About this collection
Natural Product Reports is delighted to present a themed issue dedicated to biosynthetic assembly line. Guest-edited by Professors Greg Challis and Barrie Wilkinson, the collection features contributions from leaders in the field and highlights how the recent advances in understanding the enzymology and structural biology of biosynthetic assembly lines are bringing many of the underlying molecular mechanistic principles into clear view.