Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets

Omkar S. Mohite; Colton J. Lloyd; Jonathan M. Monk; Tilmann Weber; Bernhard O. Palsson

doi:10.1016/j.synbio.2022.04.011

Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets

Omkar S. Mohite, Colton J. Lloyd, Jonathan M. Monk, Tilmann Weber^*, Bernhard O. Palsson

^*Corresponding author for this work

University of Iceland

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	900-910
Number of pages	11
Journal	Synthetic and Systems Biotechnology
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.synbio.2022.04.011
Publication status	Published - 1 Sept 2022

Bibliographical note

Funding Information:
This work was supported by grants from the Novo Nordisk Foundation ( NNF20CC0035580 , NNF16OC0021746 ).

Publisher Copyright:
© 2022 The Authors

Other keywords

Colibactin
Enterobacteria
Pangenome analysis
Secondary metabolites
Secretion systems
Workflow

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10.1016/j.synbio.2022.04.011

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title = "Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets",

abstract = "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.",

keywords = "Colibactin, Enterobacteria, Pangenome analysis, Secondary metabolites, Secretion systems, Workflow",

author = "Mohite, {Omkar S.} and Lloyd, {Colton J.} and Monk, {Jonathan M.} and Tilmann Weber and Palsson, {Bernhard O.}",

note = "Funding Information: This work was supported by grants from the Novo Nordisk Foundation ( NNF20CC0035580 , NNF16OC0021746 ). Publisher Copyright: {\textcopyright} 2022 The Authors",

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AU - Mohite, Omkar S.

AU - Lloyd, Colton J.

AU - Monk, Jonathan M.

AU - Weber, Tilmann

AU - Palsson, Bernhard O.

PY - 2022/9/1

Y1 - 2022/9/1

N2 - 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.

AB - 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.

KW - Colibactin

KW - Enterobacteria

KW - Pangenome analysis

KW - Secondary metabolites

KW - Secretion systems

KW - Workflow

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M3 - Article

AN - SCOPUS:85130496380

SN - 2405-805X

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SP - 900

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JO - Synthetic and Systems Biotechnology

JF - Synthetic and Systems Biotechnology

IS - 3

ER -

Pangenome analysis of Enterobacteria reveals richness of secondary metabolite gene clusters and their associated gene sets

Abstract

Bibliographical note

Other keywords

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