Substrate recognition by the 4-hydroxytryptamine kinase PsiK in psilocybin biosynthesis.

Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l-tryptophan involves four strictly sequential modifications. The third of these, ATP-dependent phosphorylation of the intermediate 4-hydroxytryptamine, is catalysed by PsiK.

The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site.

The Psilocybe cubensis SAM-dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM and PsiM, were generated to further examine the role of Asn247 for mono- and dimethylation in PsiM.

Methyl transfer in psilocybin biosynthesis.

Psilocybin, the natural hallucinogen produced by Psilocybe ("magic") mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.

Genetic Survey of Psilocybe Natural Products.

Psilocybe magic mushrooms are best known for their main natural product, psilocybin, and its dephosphorylated congener, the psychedelic metabolite psilocin. Beyond tryptamines, the secondary metabolome of these fungi is poorly understood. The genomes of five species (P.

Ethik First - extracurricular support for medical students and young physicians facing moral dilemmas in hospital routine.

Moral value conflicts play an increasingly central role in everyday hospital life. Clinical ethics, however, is only marginally represented in the compulsory curriculum for human medicine and the additional education regulations. The aim of the Ethik First project at the University Medical Center Schleswig-Holstein, Campus Kiel is to close this gap with an extracurricular offer and to support medical students from the fifth clinical semester onward and during their practical year as well as assistant doctors in dealing with moral dilemmas in everyday hospital life.