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Stamets, P.

Publications and source records attributed to Stamets, P..

3 recordsLinked to original sources

Adaptive Resilience: Agarikon Mycelium Modulates Immune Responses and Provides Oxidative Stress Buffering in Human Immune Cells

Agarikon (Fomitopsis officinalis, syn. Laricifomes officinalis) is a fungus with millennia of traditional use across many cultures with modern research supporting the antimicrobial, antiviral, anticancer, antioxidant, and immune-modulating properties of both mycelium and fruit body. Due to the slow growth and old-growth forest habitat of agarikon fruit bodies, its mycelium represents an easily cultivated immunomodulating and stress buffering preparation, underscored by recent clinical trials of a blend of agarikon and Trametes versicolor mycelium. We investigated the transcriptomic effects of agarikon mycelium in human peripheral blood mononuclear cells (PBMCs) under both basal and LPS-stimulated conditions, alongside evaluations of antioxidant, iron chelating, and kinase binding activity. Two agarikon fractions were also assessed for effects on cell viability and proliferation and induction of select cytokine targets. Under basal conditions, agarikon mycelium selectively engaged the innate immune response through IL-1 and NF-{kappa}B axes, balanced by increases in anti-inflammatory mediators such as IL-1RA and decreases in toll-like receptor transcripts. Under LPS-stimulated conditions, this innate immune response was modified, with measured increases in immune effectors (including TLR5) observed in response to induced stress, alongside accompanying transcript decreases in cytokine pathways that can overstimulate the immune system. Overall, agarikon mycelium demonstrated a coordinated, context-dependent immune response profile, supporting its stress-buffering and immune-modulating potential and warranting continued clinical validation.

immunology↗

Genomic Characterization of the Endangered Medicinal Polypore Agarikon (Laricifomes officinalis syn. Fomitopsis officinalis)

Agarikon (Laricifomes officinalis syn. Fomitopsis officinalis) is an endangered fungus belonging to a unique lineage in the Polyporales (Basidiomycota) with a growing body of evidence supporting its medicinal value. In this study, we report the hybrid de novo assembly and annotation of the first L. officinalis nuclear and mitochondrial genome sequences, with a nuclear genome size of 28.76 Mb assembled across 66 scaffolds (51.96% GC content; BUSCO completeness of 99.4%), and a complete core mitochondrial genome size of 197.67 kb. Structural and functional annotation of the nuclear genome yielded 8,717 predicted genes including 8,604 protein-coding genes, with 310 genes in 27 biosynthetic gene clusters. We characterized the mating type loci matA and matB, consistent with a tetrapolar mating system, and identified genes encoding key enzymes involved in triterpenoid and polyketide biosynthetic pathways that lead to the production of a diverse array of secondary metabolites. Additionally, we conducted maximum likelihood phylogenomic analysis to confirm the taxonomic position of L. officinalis among 21 species in Polyporales using protein sequences for 860 shared BUSCO genes. This high-quality annotated genome of L. officinalis will serve as a foundation for further investigations into the evolutionary history of this distinct fungal lineage, provide a reference for future population genomic analyses, and elucidate mechanisms underlying the synthesis of the bioactive compounds responsible for agarikons wide-ranging medicinal benefits.

genomics↗

Phylogenomics of the psychoactive mushroom genus Psilocybe and evolution of the psilocybin biosynthetic gene cluster

Psychoactive mushrooms in the genus Psilocybe have immense cultural value and have been used for centuries in Mesoamerica. Despite a recent surge in interest in these mushrooms due to emerging evidence that psilocybin, the main psychoactive compound, is a promising therapeutic for a variety of mental illnesses, their phylogeny and taxonomy remain substantially incomplete. Moreover, the recent elucidation of the psilocybin biosynthetic gene cluster is known for only five species of Psilocybe, four of which belong to only one of two major clades. We set out to improve the phylogeny for Psilocybe using shotgun sequencing of 71 fungarium specimens, including 23 types, and conducting phylogenomic analysis using 2,983 single-copy gene families to generate a fully supported phylogeny. Molecular clock analysis suggests the stem lineage arose [~]66 mya and diversified [~]53 mya. We also show that psilocybin biosynthesis first arose in Psilocybe, with 4-5 possible horizontal transfers to other mushrooms between 40 and 22 mya. Moreover, predicted orthologs of the psilocybin biosynthetic genes revealed two distinct gene orders within the cluster that corresponds to a deep split within the genus, possibly consistent with the independent acquisition of the cluster. This novel insight may predict differences in chemistry between the two major clades of the genus, providing further resources for the development of novel therapeutics.

evolutionary biology↗