Isolation,structure and biological activity of phomafungin,a cyclic lipodepsipeptide from a widespread tropical Phoma sp. |
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Authors: | Kithsiri Herath Guy Harris Hiranthi Jayasuriya Deborah Zink Scott Smith Francisca Vicente Gerald Bills Javier Collado Antonio González Bo Jiang Jennifer Nielsen Kahn Stefan Galuska Robert Giacobbe George Abruzzo Emily Hickey Paul Liberator Deming Xu Terry Roemer Sheo B Singh |
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Institution: | 1. Natural Products Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA;2. Centro de Investigación Básica, Merck Sharp & Dohme de España, S. A., Madrid, Spain;3. Center of Fungal Genetics, Merck Frosst Canada Ltd., Montreal, Quebec, Canada;4. Infectious Disease, Merck Research Laboratories, Rahway, NJ 07065, USA |
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Abstract: | We isolated a cyclic lipodepsipeptide, phomafungin, from a Phoma sp. The distinct antifungal activity of phomafungin in the crude extract was initially discovered by mechanistic profiling in the Candida albicans fitness test. The purified compound contains a 28 member ring consisting of eight amino acids and a β-hydroxy-γ-methyl-hexadecanoic acid, and displays a broad spectrum of antifungal activity against Candida spp., Aspergillus fumigatus and Trichophyton mentagrophytes with MIC of 2–8 μg/ml, and toxicity to mice at 25 mg/kg. The linear peptide derived from opening of the lactone ring was devoid of antifungal activity as well as toxicity. Phomafungin has been identified in a number of Phoma spp. collected from Africa and the Indian and Pacific Ocean islands. |
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