Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

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

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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.

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

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Keywords

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

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