The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10–12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2–5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC₅₀ values as low as 5.82 ± 0.18 μM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.

Hericium rajendrae is an emerging species in the genus Hericium with few members. Despite being highly regarded due to its rarity, knowledge about H. rajendrae remains limited. In this study, we sequenced, de novo assembled, and annotated the complete genome of H. rajendrae NPCB A08, isolated from the Qinling Mountains in Shaanxi, China, using the Illumina NovaSeq and Nanopore PromethION technologies. Comparative genomic analysis revealed similarities and differences among the genomes of H. rajendrae, H. erinaceus, and H. coralloides. Phylogenomic analysis revealed the divergence time of the Hericium genus, while transposon analysis revealed evolutionary characteristics of the genus. Gene family variation reflected the expansion and contraction of orthologous genes among Hericium species. Based on genomic bioinformation, we identified the candidate genes associated with the mating system, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Furthermore, metabolite profiling and comparative gene clusters analysis provided strong evidence for the biosynthetic pathway of erinacines in H. rajendrae. This work provides the genome of H. rajendrae for the first time, and enriches the genomic content of the genus Hericium. These findings also facilitate the application of H. rajendrae in complementary drug research and functional food manufacturing, advancing the field of pharmaceutical and functional food production involving H. rajendrae.

Pappia fissilis is a white-rot fungus capable of colonizing lignocellulosic substrates and decomposing plant cell wall components, and is likely involved in the degradation of woody debris and carbon cycling in forest ecosystems. A variety of lanostane-type triterpenoids and other bioactive compounds have been isolated from its fruiting bodies, pointing to potential value in natural product development. However, previous studies on this species have been largely confined to taxonomy, mitochondrial genomics, and chemical profiling of fruiting bodies, leaving its genomic features and the genetic underpinnings of wood decay and secondary metabolism poorly characterized. Here, we leveraged a hybrid sequencing strategy combining PacBio HiFi, Illumina, and Hi-C data to generate a chromosome-level genome assembly and annotation for P. fissilis, and conducted comprehensive phylogenomic, comparative genomic, CYP450, CAZyme, and biosynthetic gene cluster (BGC) analyses, which report the first genome resource for this species. The assembled genome spans 38.63 Mb, with 97.52% of the sequence anchored to 11 chromosomes, a BUSCO completeness of 95.4%, and 9499 predicted protein-coding genes. Phylogenomic analysis recovered P. fissilis as sister to a clade comprising Phlebia radiata and P. brevispora, with an estimated divergence time of approximately 53.17 Mya. The genome contains 153 CYP450 genes, 436 CAZyme genes, and 26 candidate BGCs harboring a total of 30 core biosynthetic genes (22 terpene, 5 T1PKS, 1 T3PKS, 2 $\beta$-lactone); these core genes are predominantly associated with terpene biosynthesis, and also encompass diverse types of polyketide synthase (PKS) genes as well as genes implicated in $\beta$-lactone biosynthesis. Collectively, these results establish a chromosome-level reference for investigating the genome evolution, wood-decay ecology, and secondary metabolic potential of P. fissilis, and lay the groundwork for future functional characterization of candidate biosynthetic genes and their associated natural products.