Expanding antibiotic chemical space through precursor-directed biosynthesis

Mahmud Morshed, Daniel Vuong, Andrew Crombie, Ernest Lacey, Andrew Piggott

Research output: Contribution to conferencePoster

Abstract

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 antitumour activities. Based on these bioassay results, a structure-activity relationship for the nidulin pharmacophore was proposed.
Original languageEnglish
Pages56
Number of pages1
Publication statusPublished - 30 Nov 2016
EventThe Royal Australian Chemical Institute NSW Organic Chemistry Group Annual One-Day Symposium (37th : 2016) - Sydney, Australia
Duration: 30 Nov 201630 Nov 2016

Conference

ConferenceThe Royal Australian Chemical Institute NSW Organic Chemistry Group Annual One-Day Symposium (37th : 2016)
CitySydney, Australia
Period30/11/1630/11/16

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    Morshed, M., Vuong, D., Crombie, A., Lacey, E., & Piggott, A. (2016). Expanding antibiotic chemical space through precursor-directed biosynthesis. 56. Poster session presented at The Royal Australian Chemical Institute NSW Organic Chemistry Group Annual One-Day Symposium (37th : 2016), Sydney, Australia, .