Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

Sylvia Soldatou, Grimur Hjorleifsson Eldjarn, Alejandro Huerta-Uribe, Simon Rogers, Katherine Duncan

Research output: Contribution to journalArticle

Abstract

Secondary metabolites can be viewed as a chemical language, facilitating communication between microorganisms. From an ecological point of view, this metabolite exchange is in constant flux due to evolutionary and environmental pressures. From a biomedical perspective, the chemistry is unsurpassed for its antibiotic properties. Genome sequencing of microorganisms has revealed a large reservoir of Biosynthetic Gene Clusters (BGCs); however, linking these to the secondary metabolites they encode is currently a major bottleneck to chemical discovery. This linking of genes to metabolites with experimental validation will aid the elicitation of silent or cryptic (not expressed under normal laboratory conditions) BGCs. As a result, this will accelerate chemical dereplication, our understanding of gene transcription and provide a comprehensive resource for synthetic biology. This will ultimately provide an improved understanding of both the biosynthetic and chemical space. In recent years, integrating these complex metabolomic and genomic data sets has been achieved using a spectrum of manual and automated approaches. In this review, we cover examples of these approaches, while addressing current challenges and future directions in linking these data sets.

LanguageEnglish
Article numberfnz142
Number of pages8
JournalFEMS Microbiology Letters
Volume366
Issue number13
Early online date28 Jun 2019
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint

Multigene Family
Synthetic Biology
Metabolomics
Genes
Language
Communication
Genome
Anti-Bacterial Agents
Pressure
Datasets
Direction compound

Keywords

  • secondary metabolites
  • specialised metabolites
  • biosynthetic gene clusters
  • genome mining
  • comparative metabolomics

Cite this

Soldatou, Sylvia ; Eldjarn, Grimur Hjorleifsson ; Huerta-Uribe, Alejandro ; Rogers, Simon ; Duncan, Katherine. / Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery. In: FEMS Microbiology Letters . 2019 ; Vol. 366, No. 13.
@article{c1dadd26cbdf46779299b58bb4a5581f,
title = "Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery",
abstract = "Secondary metabolites can be viewed as a chemical language, facilitating communication between microorganisms. From an ecological point of view, this metabolite exchange is in constant flux due to evolutionary and environmental pressures. From a biomedical perspective, the chemistry is unsurpassed for its antibiotic properties. Genome sequencing of microorganisms has revealed a large reservoir of Biosynthetic Gene Clusters (BGCs); however, linking these to the secondary metabolites they encode is currently a major bottleneck to chemical discovery. This linking of genes to metabolites with experimental validation will aid the elicitation of silent or cryptic (not expressed under normal laboratory conditions) BGCs. As a result, this will accelerate chemical dereplication, our understanding of gene transcription and provide a comprehensive resource for synthetic biology. This will ultimately provide an improved understanding of both the biosynthetic and chemical space. In recent years, integrating these complex metabolomic and genomic data sets has been achieved using a spectrum of manual and automated approaches. In this review, we cover examples of these approaches, while addressing current challenges and future directions in linking these data sets.",
keywords = "secondary metabolites, specialised metabolites, biosynthetic gene clusters, genome mining, comparative metabolomics",
author = "Sylvia Soldatou and Eldjarn, {Grimur Hjorleifsson} and Alejandro Huerta-Uribe and Simon Rogers and Katherine Duncan",
year = "2019",
month = "7",
day = "1",
doi = "10.1093/femsle/fnz142",
language = "English",
volume = "366",
journal = "FEMS Microbiology Letters",
issn = "0378-1097",
number = "13",

}

Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery. / Soldatou, Sylvia ; Eldjarn, Grimur Hjorleifsson ; Huerta-Uribe, Alejandro; Rogers, Simon; Duncan, Katherine.

In: FEMS Microbiology Letters , Vol. 366, No. 13, fnz142, 01.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

AU - Soldatou, Sylvia

AU - Eldjarn, Grimur Hjorleifsson

AU - Huerta-Uribe, Alejandro

AU - Rogers, Simon

AU - Duncan, Katherine

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Secondary metabolites can be viewed as a chemical language, facilitating communication between microorganisms. From an ecological point of view, this metabolite exchange is in constant flux due to evolutionary and environmental pressures. From a biomedical perspective, the chemistry is unsurpassed for its antibiotic properties. Genome sequencing of microorganisms has revealed a large reservoir of Biosynthetic Gene Clusters (BGCs); however, linking these to the secondary metabolites they encode is currently a major bottleneck to chemical discovery. This linking of genes to metabolites with experimental validation will aid the elicitation of silent or cryptic (not expressed under normal laboratory conditions) BGCs. As a result, this will accelerate chemical dereplication, our understanding of gene transcription and provide a comprehensive resource for synthetic biology. This will ultimately provide an improved understanding of both the biosynthetic and chemical space. In recent years, integrating these complex metabolomic and genomic data sets has been achieved using a spectrum of manual and automated approaches. In this review, we cover examples of these approaches, while addressing current challenges and future directions in linking these data sets.

AB - Secondary metabolites can be viewed as a chemical language, facilitating communication between microorganisms. From an ecological point of view, this metabolite exchange is in constant flux due to evolutionary and environmental pressures. From a biomedical perspective, the chemistry is unsurpassed for its antibiotic properties. Genome sequencing of microorganisms has revealed a large reservoir of Biosynthetic Gene Clusters (BGCs); however, linking these to the secondary metabolites they encode is currently a major bottleneck to chemical discovery. This linking of genes to metabolites with experimental validation will aid the elicitation of silent or cryptic (not expressed under normal laboratory conditions) BGCs. As a result, this will accelerate chemical dereplication, our understanding of gene transcription and provide a comprehensive resource for synthetic biology. This will ultimately provide an improved understanding of both the biosynthetic and chemical space. In recent years, integrating these complex metabolomic and genomic data sets has been achieved using a spectrum of manual and automated approaches. In this review, we cover examples of these approaches, while addressing current challenges and future directions in linking these data sets.

KW - secondary metabolites

KW - specialised metabolites

KW - biosynthetic gene clusters

KW - genome mining

KW - comparative metabolomics

UR - https://academic.oup.com/femsle/issue

U2 - 10.1093/femsle/fnz142

DO - 10.1093/femsle/fnz142

M3 - Article

VL - 366

JO - FEMS Microbiology Letters

T2 - FEMS Microbiology Letters

JF - FEMS Microbiology Letters

SN - 0378-1097

IS - 13

M1 - fnz142

ER -