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Docking domain-mediated subunit interactions in natural product megasynth(et)ases
Helen G Smith1,2, Matthew J Beech2, Józef R Lewandowski2
1Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Journal of Industrial Microbiology & Biotechnology
|February 28, 2021
Summary
Polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) enzymes assemble via docking domains (DDs) for natural product biosynthesis. This review examines characterized PKS and NRPS DD structures and their engineering applications.
Area of Science:
- Biochemistry and Molecular Biology
- Natural Product Biosynthesis
Background:
- Polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) are large multienzyme complexes responsible for producing valuable natural products.
- The assembly of these megasynth(et)ases requires precise organization of catalytic domains, crucial for the biosynthesis of specific metabolites.
- Docking domains (DDs) are short amino acid regions at the termini of PKS and NRPS subunits that mediate interactions for substrate transfer and pathway fidelity.
Purpose of the Study:
- To review all structurally characterized examples of NRPS and PKS docking domains.
- To summarize current efforts in utilizing docking domains for the engineering of biosynthetic pathways.
Main Methods:
- Structural analysis of characterized NRPS and PKS docking domains.
- Literature review of studies on docking domain interactions and engineering applications.
Main Results:
- Compilation of structural data for various NRPS and PKS docking domains.
- Overview of successful and attempted engineering strategies leveraging docking domain interactions.
Conclusions:
- Docking domains play a critical role in the assembly and function of PKS and NRPS systems.
- Understanding PKS and NRPS docking domain structures provides a basis for rational pathway engineering to create novel natural products.
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