Journal article
Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Reconstruction, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark2
Strain Design Teams, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark3
University of California at San Diego4
Natural Products Genome Mining, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
DTU Microbes Initiative, Centers, Technical University of Denmark6
Center for Microbial Secondary Metabolites, Centers, Technical University of Denmark7
In silico genome mining provides easy access to secondary metabolite biosynthetic gene clusters (BGCs) encoding the biosynthesis of many bioactive compounds, which are the basis for many important drugs used in human medicine. However, the association between BGCs and other functions encoded in the genomes of producers have remained elusive.
Here, we present a systems biology workflow that integrates genome mining with a detailed pangenome analysis for detecting genes associated with a particular BGC. We analyzed 3,889 enterobacterial genomes and found 13,266 BGCs, represented by 252 distinct BGC families and 347 additional singletons. A pangenome analysis revealed 88 genes putatively associated with a specific BGC coding for the colon cancer-related colibactin that code for diverse metabolic and regulatory functions.
The presented workflow opens up the possibility to discover novel secondary metabolites, better understand their physiological roles, and provides a guide to identify and analyze BGC associated gene sets.
Language: | English |
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Publisher: | KeAi Publishing |
Year: | 2022 |
Pages: | 900-910 |
ISSN: | 2405805x and 20971206 |
Types: | Journal article |
DOI: | 10.1016/j.synbio.2022.04.011 |
ORCIDs: | Mohite, Omkar S. , Weber, Tilmann , Palsson, Bernhard O. , 0000-0001-6556-6345 and 0000-0002-3895-8949 |
Colibactin Enterobacteria Pangenome analysis SDG 3 - Good Health and Well-being Secondary metabolites Secretion systems Workflow
BGC, Biosynthetic gene cluster Biology (General) Biotechnology GCF, Gene cluster family NRPS, Non-ribosomal peptide synthetase PKS, Polyketide synthase QH301-705.5 RiPP, Ribosomally synthesized and post-translationally modified peptide T4SS, Type IV Secretion System T6SS, TypeVI Secretion System TP248.13-248.65