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Inter-Kingdom beach warfare: Microbial chemical communication activates natural chemical defences

The ISME Journalvolume 13pages147158 (2019) | Download Citation


An inter-kingdom beach warfare between a Streptomyces sp. and Aspergillus sp. co-isolated from shallow water beach sand, collected off Heron Island, Queensland, Australia, saw the bacteriostatic Aspergillus metabolite cyclo-(l-Phe-trans-4-hydroxy-l-Pro) (3) stimulate the Streptomyces to produce nitric oxide (NO), which in turn mediated transcriptional activation of a silent biosynthetic gene cluster (BGC) for fungistatic heronapyrrole B (1). Structure activity relationship studies, coupled with the use of NO synthase inhibitors, donors and scavangers, and both genomic and transcriptomic analyses, confirmed the extraordinary chemical cue specificity of 3, and its NO-mediated mechanism of transcriptional action. Our findings reveal the importance of inter-kingdom (fungal-bacterial) chemical communication in the regulation of silent BGCs coding for chemical defenses. We propose that the detection and characterisation of NO mediated transcriptional activation (NOMETA) of silent chemical defences in the environment, may inspire broader application in the field of microbial biodiscovery.

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ZK acknowledges the University of Queensland for a postgraduate scholarship, and PCM the Australian Department of Education and Training for an Endeavour Fellowship. We thank R Ritesh for original isolation of Streptomyces sp CMB-M0423, R Palfreyman for bioinformatic support, and the Queensland (UQ) node of Proteomics and Metabolomics Australia, a NCRIS initiative under Bioplatforms Australia Pty Ltd. Microscopy was performed at the Australian Cancer Research Foundation (ACRF) Institute for Molecular Bioscience, Cancer Biology Imaging Facility, with support from N Condon, J Springfield, M. Scott, J Griffin and K Green. This research was funded in part by the University of Queensland, Institute for Molecular Bioscience and Australian Institute for Bioengineering and Nanotechnology.

Author information


  1. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, 4072, Australia

    • Zeinab G. Khalil
    • , Pablo Cruz-Morales
    •  & Robert J. Capon
  2. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, 4072, QLD, Australia

    • Pablo Cruz-Morales
    • , Cuauhtemoc Licona-Cassani
    •  & Esteban Marcellin
  3. Centro de Biotecnología FEMSA, Tecnológico de Monterrey, NL, Mexico

    • Cuauhtemoc Licona-Cassani


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The authors declare that they have no conflict of interest.

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Correspondence to Robert J. Capon.

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