Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

Soldatou, Sylvia and Eldjarn, Grimur Hjorleifsson and Huerta-Uribe, Alejandro and Rogers, Simon and Duncan, Katherine (2019) Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery. FEMS Microbiology Letters, 366 (13). fnz142. ISSN 0378-1097

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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.

    ORCID iDs

    Soldatou, Sylvia, Eldjarn, Grimur Hjorleifsson, Huerta-Uribe, Alejandro, Rogers, Simon and Duncan, Katherine ORCID logoORCID: https://orcid.org/0000-0002-3670-4849;
    • Item type:Article
      ID code:68558
      Dates:
      Date
      Event
      1 July 2019
      Published
      28 June 2019
      Published Online
      17 June 2019
      Accepted
      Keywords:secondary metabolites, specialised metabolites, biosynthetic gene clusters, genome mining, comparative metabolomics, Pharmacy and materia medica, Pharmacology, Toxicology and Pharmaceutics(all)
      Subjects:Medicine > Pharmacy and materia medica
      Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
      Depositing user: Pure Administrator
      Date deposited:20 Jun 2019 15:34
      Last modified:23 Sep 2021 07:18
      Related URLs:
      URI:https://strathprints.strath.ac.uk/id/eprint/68558
    CORE (COnnecting REpositories)