Planta Med 2012; 78 - PI63
DOI: 10.1055/s-0032-1320750

Structure and biological activity of a cyclic lipodepsipeptide phaeofungin discovered with the Candida albicans fitness test

J Ondeyka 1, G Harris 1, K Herath 1, D Zink 1, F Vicente 2, 4, G Bills 2, 4, J Collado 2, G Platas 2, 4, A González de Val 2, B Jiang 3, J Nielsen Kahn 1, S Galuska 1, R Giacobbe 1, G Abruzzo 1, E Hickey 1, P Liberator 1, D Xu 3, T Roemer 3, S Singh 1
  • 1Merck Research Laboratories, Rahway, NJ, USA
  • 2Merck Sharp & Dohme de España, Madrid, Spain
  • 3Merck Frosst Canada, Montreal, Quebec, Canada
  • 4Fundación MEDINA, Armilla, Granada, Spain

Phaeofungin, a cyclic lipodepsipeptide, was isolated from a fermentation a Phaeosphaeria sp. (Phaeosphaeriaceae) from Spain. Antibiosis of the extract was recognized in an assay for C. albicans cell-wall perturbing agents. The extracts were chemogenomically assayed in the C. albicans fitness test (CaFT) that profiles the activities of antifungal agents. The CaFT profile overlapped with, but was differentiated from that of an antifungal lipodepsipeptide, phomafungin. Differences were confirmed when structure of phaeofungin was elucidated by spectroscopic methods including HRFTMS and 2D NMR. The amino acid identity and configuration were confirmed by acid hydrolysis followed by Marfey's derivatization. The antifungal activities of both lipodepsipeptides demonstrated phaeofungin synergizes with aureobasidin A and caspofungin leading to ATP leakage from cells of C. albicans.