Chemistry and biology of Malassezia metabolites related to skin diseases
Malassezia yeasts are symbiotic to human skin and can become pathogenic under currently insufficiently understood conditions. During the last years several works have contributed to the description of the metabolome of Malassezia yeasts. Previously [1,2] we compared Malassezia furfur isolates from healthy and seborrhoic dermatitis skin for the production of indole derivatives and identified the preferential biosynthesis of malassezin, indolo[3,2-b]carbazol (ICZ) and indirubin by M. furfur strains isolated from diseased skin. Ongoing study revealed that tryptanthrin is also a yet undescribed Malassezia metabolite. The simultaneous production of three metabolites (ICZ, indirubin and tryptanthrin) which are among the most active known Aryl hydrocarbon receptor (AhR) inducers is a fascinating finding which boosts the interest about this yeast and strengthens its relation with serious skin diseases. Interestingly, a previously reported by us  biomimetic synthesis of indirubin by one step oxidation of indol-3-carboxaldehyde (I3A) using hydrogen peroxide, leads also simultaneously to one step formation of tryptanthrin. This evident reveals the common biosynthetic origin of indirubin and tryptanthrin from I3A which is a common tryptophan metabolite found in all Malassezia studied species. Although, AhR is an orphan receptor, there is increasing data about its relation with skin homeostasis and skin nosology. Ongoing and previous work on the activation of AhR in HaCaT cells by Malassezia extracts  point to a significant role of Malassezia synthesized potent AhR ligands in the development of skin diseases.
References: 1. Gaitanis, G. et al. (2008)J. Invest. Dermatol. 128:1620–1625.
2. Giakoumaki, D. et al. (2008) Planta Med. 74: 1081.
3. Magiatis, P. et al (2009) Planta Med. 75: 912.