Genomic mining and diversity of assembly line polyketide synthases

Author:

Kishore Shreya1ORCID,Khosla Chaitan123

Affiliation:

1. Department of Chemistry, Stanford University, Stanford, CA 94305, USA

2. Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA

3. Sarafan ChEM-H, Stanford University, Stanford, CA 94305, USA

Abstract

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.

Funder

NIH

Publisher

The Royal Society

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience

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