Generation of Indole Alkaloids in the Human-Pathogenic Fungus Exophiala dermatitidis

• Published in: European Journal of Organic Chemistry 2010-04, Vol.2010 (11), p.2084-2090
• Main Authors: Kindler, Bernhard L. J., Krämer, Hans-Joachim, Nies, Silke, Gradicsky, Philipp, Haase, Gerhard, Mayser, Peter, Spiteller, Michael, Spiteller, Peter
• Format: Article
• Language: English
• Subjects: Alkaloids; Chemistry; Condensed benzenic and aromatic compounds; Exact sciences and technology; Fungi; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Melanin; Mycosis; Natural products; Organic chemistry; Preparations and properties
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200901311

Exophialin, a previously unknown indole alkaloid, was isolated from the human‐pathogenic fungus Exophiala dermatitidis upon cultivation on a medium containing tryptophan as sole nitrogen source. Its structure has been elucidated by 1D and 2D NMR experiments and mass spectrometry. When the mutant strain Mel‐1 was used in place of the wild‐type strain, the new indole alkaloid 8‐hydroxyexophialin was generated instead of exophialin. This result indicates that the aromatic moiety of exophialin originates from 2‐hydroxyjuglone, a shunt product of the 1,8‐dihydroxynaphthalene melanin biosynthesis, which is only produced by the wild‐type strain,but not by the mutant. In contrast, the mutant accumulatesflavioline, which acts as precursor leading to the generation of 8‐hydroxyexophialin instead of exophialin. A new type of indole alkaloids, containing an aromatic pentaketide moiety has been isolated from cultures of the black yeast‐like fungus Exophiala dermatitidis upon cultivation on a medium containing tryptophan as sole amino acid. While the wild‐type strain produces exophialin, the mutant Mel‐1 generates 8‐hydroxyexophialin, suggesting that exophialin originates partially from 2‐hydroxyjuglone.