Janis Fricke

Insempra GmbH

Macrotermitinae termites have farmed fungi in the genus Termitomyces as a food source for millions of years. However, the biochemical mechanisms orchestrating this mutualistic relationship are largely unknown. To deduce fungal signals and ecological patterns that relate to the stability of this symbiosis, we explored the volatile organic compound (...

Characterizing ancient clades of fungal symbionts is necessary for understanding the evolutionary process underlying symbiosis development. In this study, we investigated a distinct subgeneric taxon of Xylaria (Xylariaceae), named Pseudoxylaria, whose members have solely been isolated from the fungus garden of farming termites. Pseudoxylaria are in...

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. azurescens , P. cubensis , P. cyanescens , P. mexicana , and P. serbica ) were...

Macrotermitinae termites have domesticated fungi of the genus Termitomyces as food for their colony, analogously to human farmers growing crops. Termites propagate the fungus by continuously blending foraged and predigested plant material with fungal mycelium and spores (fungus comb) within designated subterranean chambers. To test the hypothesis t...

Insights into the genomic consequences of symbiosis for basidiomycete fungi associated with social insects remain sparse. Capitalising on viability of spores from centuries-old herbarium specimens of free-living, facultative and specialist termite-associated Podaxis fungi, we obtained genomes of 10 specimens, including two type species described by...

Targeted HRMS2-GNPS-based metabolomic analysis of Pseudoxylaria sp. X187, a fungal antagonist of the fungus-growing termite symbiosis, resulted in the identification of two lipopeptidic congeners of xylacremolides, named xylacremolide C and D, which are built from d-phenylalanine, l-proline and an acetyl-CoA starter unit elongated by four malonyl-C...

A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from Psilocybe cubensis, chemically synthesized 5-methylpsilocin (2) was enzymatically phosphorylated to provide 5-methylpsilocybin (1). The zwitterionic product was isolated from th...

Insights into the genomic consequences of symbiosis for basidiomycete fungi associated with social insects remain sparse. Capitalising on viability of spores from centuries-old herbarium specimens of free-living, facultative and specialist termite-associated Podaxis fungi, we obtained genomes of 10 specimens, including two type species described by...

Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment‐resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis by the mush...

Psychotropic Psilocybe mushrooms biosynthesize their principal natural product psilocybin in five steps, among them a phosphotransfer‐ and two methyltransfer reactions, which consume one equivalent of 5´‐adenosyl‐triphosphate (ATP) and two equivalents of S‐adenosyl‐l‐methionine (SAM). This short but cosubstrate‐intensive pathway requires nucleoside...

The psychotropic effects of Psilocybe “magic” mushrooms are caused by the L‐tryptophan‐derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other L‐tryptophan‐derived β‐carbolines as their n...

Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently investigated in advanced clinical trials. Here, we report on a biocatalytic route to synthesize 6‐methylated psilocybin and baeocystin fr...

Psilocybe mushrooms are best known for their L‐tryptophan‐derived psychotropic alkaloid psilocybin. The dimethylation of its precursor norbaeocystin by the enzyme PsiM is a critical step during its biosynthesis. However, the "magic" mushroom Psilocybe serbica also mono‐ and dimethylates L‐tryptophan, which is incompatible with the specificity of Ps...

The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4‐phosphoryloxy‐N,N‐dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analog, psilocin. The colloquial term "magic mushrooms" for these fungi alludes to their hallucinogenic effects and to their use as recr...

Psilocybin (4‐phosphoryloxy‐N,N‐dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe, the so‐called "magic mushrooms". The pharmaceutical interest in this psychotropic natural product as a future medication to treat depression and anxiety is strongly re‐emerging. Here, we present an enhanced enzymatic route of psilocybin productio...

Heterologous expression of multi-gene biosynthetic pathways in eukaryotic hosts is limited by highly regulated individual monocistrons. Dissimilar to prokaryotes, each eukaryotic gene is strictly controlled by its own regulatory elements, such as promoter and terminator. Consequently, parallel transcription can occur only when a group of genes is s...

Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called "magic mushrooms". Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes. These include i) PsiD which represents a new class of fu...

Psilocybin ist der psychotrope, vom Tryptamin abgeleitete Naturstoff der Psilocybe-Fruchtkçrper, der so genannten “Zauberpilze”. Obwohl dessen Struktur seit 60 Jahren bekannt ist, blieb die enzymatische Grundlage ihrer Biosynthese ungekl?rt. Wir charakterisierten vier Psi- locybin-Biosyntheseenzyme, n?mlich i) PsiD, welches zu einer neuen Klasse pi...

The prenylphenols are a class of natural products that have been frequently isolated from basidiomycetes, e.g., from the genus Stereum (false turkey tail fungi) and other Russulales as well as from ascomycetes. Biosynthetically, these compounds are considered hybrids, as the orsellinic acid moiety is a polyketide and the prenyl side chain originate...