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Review Article

Future directions for the discovery of antibiotics from actinomycete bacteria

Rebecca Devine, Matthew I. Hutchings, Neil A. Holmes
Emerging Topics in Life Sciences Apr 04, 2017, ETLS20160014; DOI: 10.1042/ETLS20160014
Rebecca Devine
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
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Matthew I. Hutchings
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
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  • For correspondence: m.hutchings@uea.ac.ukn.holmes@uea.ac.uk
Neil A. Holmes
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
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  • For correspondence: m.hutchings@uea.ac.ukn.holmes@uea.ac.uk
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Abstract

Antimicrobial resistance (AMR) is a growing societal problem, and without new anti-infective drugs, the UK government-commissioned O'Neil report has predicted that infectious disease will claim the lives of an additional 10 million people a year worldwide by 2050. Almost all the antibiotics currently in clinical use are derived from the secondary metabolites of a group of filamentous soil bacteria called actinomycetes, most notably in the genus Streptomyces. Unfortunately, the discovery of these strains and their natural products (NPs) peaked in the 1950s and was then largely abandoned, partly due to the repeated rediscovery of known strains and compounds. Attention turned instead to rational target-based drug design, but this was largely unsuccessful and few new antibiotics have made it to clinic in the last 60 years. In the early 2000s, however, genome sequencing of the first Streptomyces species reinvigorated interest in NP discovery because it revealed the presence of numerous cryptic NP biosynthetic gene clusters that are not expressed in the laboratory. Here, we describe how the use of new technologies, including improved culture-dependent and -independent techniques, combined with searching underexplored environments, promises to identify a new generation of NP antibiotics from actinomycete bacteria.

  • AMR
  • antibiotics
  • Streptomyces
  • Abbreviations

    AMR,
    antimicrobial resistance;
    BGCs,
    biosynthetic gene clusters;
    CDA,
    calcium-dependent antibiotic;
    eDNA,
    environmental DNA;
    HDAC,
    histone deacetylase;
    MRSA,
    methicillin-resistant Staphylococcus aureous;
    NP,
    natural product;
    NRPS,
    non-ribosomal peptide synthetase;
    PKS,
    polyketide synthase;
    ppGpp,
    guanosine tetraphosphate;
    RiPPs,
    ribosomally synthesised and post-translationally modified peptides;
    VRE,
    vancomycin-resistant enterococci.
    • Received January 18, 2017.
    • Revision received February 3, 2017.
    • Accepted February 9, 2017.
    • © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society and the Royal Society of Biology
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    Future directions for the discovery of antibiotics from actinomycete bacteria
    Rebecca Devine, Matthew I. Hutchings, Neil A. Holmes
    Emerging Topics in Life Sciences Apr 2017, ETLS20160014; DOI: 10.1042/ETLS20160014
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    Future directions for the discovery of antibiotics from actinomycete bacteria
    Rebecca Devine, Matthew I. Hutchings, Neil A. Holmes
    Emerging Topics in Life Sciences Apr 2017, ETLS20160014; DOI: 10.1042/ETLS20160014

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    • Article
      • Abstract
      • Introduction
      • Control of antibiotic production in actinomycetes
      • Genome mining for novel BGCs
      • Searching for new strains in underexplored environments
      • Concluding remarks
      • Competing Interests
      • References
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    Keywords

    AMR
    antibiotics
    Streptomyces

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