As the main nitrogen source in Malassezia furfur, tryptophan induces the formation of fluorochromes and pigments, which make the yeast less sensitive to UV light. To detect a chemical UV filter, M. furfur (CBS 1878) was incubated at 30 degrees C for 14 days on a pigment-inducing medium and agar extracts were purified by column chromatography, preparative TLC and HPLC. Structural analysis of the pure metabolites was performed by mass spectroscopy and NMR. A yellow compound eluting from the column with 64% acetonitrile was found to be a potential UV filter because of its broad UV absorption (lambda(max) 389, 315, 289, 212 nm). It was an indole derivative (C(20)H(13)N(3)O; pityriacitrin) which had recently been shown to be a potent UV filter in bacteria. Its UV protective properties were confirmed in a yeast model and also in humans. Pityriasis versicolor induced by Malassezia yeasts is characterized by depigmented skin areas showing reduced melanin synthesis but no increased UV sensitivity. This UV protection might be explained by the presence of pityriacitrin which is produced by M. furfur.

Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. Pityriasis versicolor is often accompanied by a long-lasting depigmentation that persists even after successful antimycotic therapy. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the depigmentation process. We now report that human melanocytes undergo apoptosis when exposed to the crude mixture of tryptophan metabolites from M. furfur. The active compound was identified as malassezin, previously isolated by us from the same source and characterized as an agonist of the aryl hydrocarbon (Ah) receptor. The compound could, therefore, contribute to the marked depigmentation observed during the course of pityriasis versicolor.

Eleven new indole alkaloids were isolated from cultures of the human pathogenic yeast Malassezia furfur after addition of L‐tryptophan as the sole N‐source: pityriacitrin B (2), the malassezindoles A (3) and B (4), malassezialactic acid (6), the malasseziazoles A (7), B (8), and C (9), pityriazole (10), malasseziacitrin (11), and malassezione (12), along with the known d‐indole‐3‐lactic acid (=(αR)‐α‐hydroxy‐1H‐indole‐3‐propanoic acid 5), and 2‐hydroxy‐1‐(1H‐indol‐3‐yl)ethanone (13). The structural elucidation of these compounds was performed by spectroscopic methods (MS as well as 1D‐ and 2D‐NMR). The biogenetic relationships (Scheme) and biological activities of the new metabolites are discussed.

Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthdayEleven new indole alkaloids were isolated from cultures of the human pathogenic yeast Malassezia furfur after addition of l-tryptophan as the sole N-source: pityriacitrin B (2), the malassezindoles A (3) and B (4), malassezialactic acid (6), the malasseziazoles A (7), B (8), and C (9), pityriazole (10), malasseziacitrin (11), and malassezione (12), along with the known d-indole-3-lactic acid ( (aR)-a-hydroxy-1H-indole-3-propanoic acid 5), and 2-hydroxy-1-(1H-indol-3-yl)ethanone (13). The structural elucidation of these compounds was performed by spectroscopic methods (MS as well as 1D-and 2D-NMR). The biogenetic relationships (Scheme) and biological activities of the new metabolites are discussed.

Pityriasis versicolor is the most common skin mycosis in humans worldwide. Yeasts of the genus Malassezia, particularly M. furfur, a saprophyte occurring widely on human skin, are generally regarded as the causative agents. M. furfur is able to convert tryptophan into a variety of indole alkaloids, some of them showing biological properties that correlate well with certain clinical features of pityriasis versicolor. This suggests a possible role for these compounds in the pathophysiology of the disease. We here report that the novel pityriarubins A, B and C, isolated from cultures of the yeast, inhibit respiratory burst in human neutrophils, activated by various agents, in a highly selective, unexpected manner. The release of 5-lipoxygenase products after challenge of neutrophils with the calcium ionophore A23187 is also inhibited in a dose-dependent manner. These activities reflect the close structural relationship of pityriarubins to bisindolylmaleimides, which have recently gained great interest as protein kinase inhibitors.