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Bioactivity-Guided Metabolite Profiling of Feijoa (Acca sellowiana) Cultivars Identifies 4‑Cyclopentene-1,3-dione as a Potent Antifungal Inhibitor of Chitin Synthesis

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journal contribution
posted on 16.03.2018, 00:00 by Mona Mokhtari, Michael D. Jackson, Alistair S. Brown, David F. Ackerley, Nigel J. Ritson, Robert A. Keyzers, Andrew B. Munkacsi
Pathogenic fungi continue to develop resistance against current antifungal drugs. To explore the potential of agricultural waste products as a source of novel antifungal compounds, we obtained an unbiased GC-MS profile of 151 compounds from 16 commercial and experimental cultivars of feijoa peels. Multivariate analysis correlated 93% of the compound profiles with antifungal bioactivities. Of the 18 compounds that significantly correlated with antifungal activity, 5 had not previously been described from feijoa. Two novel cultivars were the most bioactive, and the compound 4-cyclopentene-1,3-dione, detected in these cultivars, was potently antifungal (IC50 = 1–2 μM) against human-pathogenic Candida species. Haploinsufficiency and fluorescence microscopy analyses determined that the synthesis of chitin, a fungal-cell-wall polysaccharide, was the target of 4-cyclopentene-1,3-dione. This fungal-specific mechanism was consistent with a 22–70-fold reduction in antibacterial activity. Overall, we identified the agricultural waste product of specific cultivars of feijoa peels as a source of potential high-value antifungal compounds.