Genomic and Metabolomic Analyses of the Medicinal Fungus Inonotus hispidus for Its Metabolite’s Biosynthesis and Medicinal Application

Abstract

Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing.

Secondary Metabolites of Bird’s Nest Fungi: Chemical Structures and Biological Activities

“…And cordycepin, a nucleoside metabolite, is the active medicinal compound of Cordyceps species . However, cyathane diterpenoids, the active constituents of the bird’s nest fungus, are not only derived from the genus Cyathus but are also common in the Hericium mushrooms and other fungi. − , Similarly, styrylpyrone compounds, a group of pale yellow active compounds, are widely present in mushrooms belonging to the genera Inonotus and Phellinus of the family Geomycetaceae. ,− …”

Mushroom-Derived Compounds as Metabolic Modulators in Cancer

“…Currently, 270 species of mushrooms are reported to be potentially useful for human health and the mushrooms credited with success against neoplasia belong to the genus Agaricus , Albatrellus , Antrodia , Calvatia , Clitocybe , Cordyceps , Flammulina , Fomes , Funlia , Ganoderma , Inocybe , Inonotus , Lactarius , Laetiporus , Phellinus , Pleurotus , Russula , Schizophyllum , Suillus , Trametes , and Xerocomus , and compounds isolated from these mushrooms have targeted each of the cancer hallmarks recently listed by Hanahan and Weinberg [ 50 ] in tumour cell systems and animal assays [ 51 , 52 , 53 , 54 , 55 , 56 ]. For example, Kang et al [ 57 ] have demonstrated that ergosterol peroxide isolated from Inonotus obliquus inhibited the growth of human colorectal cancer cell lines HCT116, HT-29, SW620, and DLD-1 by suppressing the nuclear levels of beta-catenin which ultimately resulted in reduced transcription of c-MYC, cyclin D1, and cyclin-dependent kinase-8 ( Figure 2 ).…”

Whole genome sequencing and analysis of Inonotus hispidus isolated from the Chengde Mountain Resort, China

“…Fungi have also been used as model organisms to explore problems in eukaryotic cell biology and genetics, and to tackle speci c biological problems related to plant pathology and medicine (Datta, Ganesan et al 1990, Dean, Talbot et al 2005. With the rapid development of high-throughput sequencing technology, fungi can now be identi ed and classi ed at a genome-wide level and their secondary metabolites and medicinal properties of the fungi can also be analyzed and studied at the level of whole genome (Tang, Jin et al 2022, Zhang, Feng et al 2022. Currently (April 16, 2024), 17,762 fungal genomes have been analyzed and deposited at the National Center for Biotechnology Information (https://www.ncbi.nlm.nih.gov/data-hub/taxonomy/4751/); most of the collected genomes belong to the phylum Ascomycota (14,320, 80.62%), followed by Basidiomycota (2,585, 14.55%) (NCBI 2022).…”

“…The I. hispidus strain from Chengde used in this study was isolated from a mulberry tree over 300 years old at the Chengde Mountain Resort, giving this strain signi cant historical and research value. Although the I. hispidus strains of Aksu (Xinjiang), Harbin (Heilongjiang), Xiajin (Shandong), and Linqing (Shandong) have been sequenced, whole genome sequencing of the I. hispidus strain from Chengde Mountain Resort still has great signi cance for studying the genomic and functional differences of I. hispidus from different regions, and to enrich the genomic diversity of I. hispidus (Tang, Jin et al 2022, Zhang, Feng et al 2022, Jinglin 2023, Wang, Bao et al 2023). In addition, access to genomic information on I. hispidus "CDMR" strain can contribute to genetic and genomic research on its nutritional and therapeutic traits.…”