Abstract
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.