Expanding antibiotic chemical space through precursor-directed biosynthesis

M. T. Morshed, D. Vuong, A. Crombie, E. Lacey, A. Piggott

    Research output: Chapter in Book/Report/Conference proceedingConference proceeding contribution


    Nidulin is a fungal depsidone antibiotic first isolated in 1944 from the fungus Aspergillus nidulans. Nidulin shows potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have employed a combination of natural products chemistry, precursor-directed biosynthesis and chemical derivatisation to expand chemical space around the nidulin pharmacophore. Initial optimisation of culture media led to two new fungal metabolites, 7-carboxyfolipastatin and unguinolic acid, as well as four previously reported compounds. In precursor-directed biosynthesis experiments, Aspergillus unguis was supplemented with halide salts, leading to three new depsides, unguidepside A, unguidepside B and 5-bromoagonodepside B, and one new depsidone, 2-bromo-7-chlorounguinol. Finally, a semi-synthetic approach was employed to generate six nidulin analogues. All natural, unnatural and semi-synthetic compounds were screened for antibacterial, antifungal and cell cytotoxicity activities. Based on these bioassay results, a structure-activity relationship for the nidulin pharmacophore was proposed.
    Original languageEnglish
    Title of host publicationRACI National Centenary Conference 2017
    Subtitle of host publicationabstract book
    Place of PublicationSydney
    PublisherICMS Australasia
    Number of pages1
    Publication statusPublished - 2017
    EventRACI Centenary Congress - Melbourne Convention and Exhibition Centre, Melbourne, Australia
    Duration: 23 Jul 201728 Jul 2017


    ConferenceRACI Centenary Congress
    Internet address


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