Related Experiment Video
Updated: Jun 28, 2026
09:08
From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Genomic scale analysis of assembly-line polyketide synthase diversity and evolution
Seokyoung Lee1, Chaitan Khosla1,2,3
1Department of Chemistry, Stanford University, Stanford, California 94305, USA. khosla@stanford.edu.
Natural Product Reports
|June 26, 2026
Summary
Assembly-line polyketide synthases (PKSs) are crucial for natural product biosynthesis. Analyzing PKS sequence diversity helps decode "orphan" PKSs and understand their evolution, guiding future research.
Area of Science:
- Biochemistry and Molecular Biology
- Genomics
- Natural Product Chemistry
Background:
- Assembly-line polyketide synthases (PKSs) are vital natural catalysts for producing medicinally important compounds.
- Microbial genome sequencing has uncovered numerous
- orphan
- PKSs with unknown products, representing a vast untapped resource.
- Understanding PKS sequence diversity and evolutionary history is key to prioritizing research efforts.
Purpose of the Study:
- To create an updated, curated database (PKSClusterDB) of assembly-line PKSs.
- To develop a framework for identifying and analyzing PKS families based on conserved sequence motifs.
- To investigate lineage-dependent diversification patterns within PKS families.
Main Methods:
- Hand-curation of a large-scale PKS database (PKSClusterDB) containing 16,633 non-redundant assembly-line PKSs.
- Development of an automatable "anchor-window" framework using conserved multimodular PKS segments.
- Application of the framework to analyze PKS families and their diversification.
Main Results:
- PKSClusterDB provides a comprehensive resource for studying PKS diversity.
- The "anchor-window" framework successfully identified and interrogated PKS families.
- Observed lineage-dependent diversification patterns, revealing varying evolutionary trajectories within PKS families.
- PKSClusterDB aids in exploring PKS scaffold architecture, substrate specificity, and modular organization.
Conclusions:
- The curated PKSClusterDB and the "anchor-window" framework are valuable tools for understanding assembly-line PKS evolution and diversity.
- Lineage-specific diversification patterns offer insights into PKS functional evolution.
- Future integration of machine learning can further accelerate the discovery of PKS biosynthetic mechanisms and applications.
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