Genomic mining and diversity of assembly line polyketide synthases

Assembly line polyketide synthases (PKSs) are a large family of multifunctional enzymes responsible for synthesizing many medicinally relevant natural products with remarkable structural variety and biological activity. The decrease in cost of genomic sequencing paired with development of computatio...

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Bibliographic Details
Published in:Open biology 2023-08, Vol.13 (8), p.230096
Main Authors: Kishore, Shreya, Khosla, Chaitan
Format: Article
Language:English
Subjects:
antibiotics
Base Sequence
Biological Products
enzymatic assembly lines
Genomics
https://orphanpkscatalog2022.stanford.edu/catalog
natural products
polyketide synthase
Polyketide Synthases - chemistry
Polyketide Synthases - genetics
Polyketide Synthases - metabolism
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Summary:Assembly line polyketide synthases (PKSs) are a large family of multifunctional enzymes responsible for synthesizing many medicinally relevant natural products with remarkable structural variety and biological activity. The decrease in cost of genomic sequencing paired with development of computational tools like antiSMASH presents an opportunity to survey the vast diversity of assembly line PKS. Mining the genomic data in the National Center for Biotechnology Information database, our updated catalogue (https://orphanpkscatalog2022.stanford.edu/catalog) presented in this article revealed 8799 non-redundant assembly line polyketide synthase clusters across 4083 species, representing a threefold increase over the past 4 years. Additionally, 95% of the clusters are 'orphan clusters' for which natural products are neither chemically nor biologically characterized. Our analysis indicates that the diversity of assembly line PKSs remains vastly under-explored and also highlights the promise of a genomics-driven approach to natural product discovery.
ISSN:2046-2441
2046-2441
DOI:10.1098/rsob.230096