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

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.

Chromosome-Level Genome Sequences, Comparative Genomic Analyses, and Secondary-Metabolite Biosynthesis Evaluation of the Medicinal Edible Mushroom Laetiporus sulphureus.

Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.

Anti-cancer Mechanism of Polygonati Rhizoma-Lilii Bulbus Based on Network Pharmacology / 中国实验方剂学杂志

Objective::To screen out active ingredients of Polygonati Rhizoma-Lilii Bulbus, and predict the targets and signaling pathways, in order to explore the potential mechanism in treatment of cancer by using network pharmacology. Method::All of active ingredients and targets of Polygonati Rhizoma-Lilii Bulbus were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease targets for cancer were collected through databases of gene-disease associations (DisGeNET) and Online Mendelian Inheritance in Man (OMIM). Then the Omicshare platform was used to match the active ingredients and the targets for treating cancer. And the " drug-active ingredients-disease targets" network was established using Cytoscape 3.7.0 software. The functional protein association networks (String) database was used to construct the protein interaction network of drug pair targets for treating cancer. Finally, the Functional Annotation Bioinformatics Microarray Analysis (DAVID) database was used to analyze the biological functions and metabolic pathways of key targets. Result::A total of 19 active ingredients were screened out, 234 targets were predicted, 6 active ingredients were identified to be related to cancer. The anti-cancer effect was mainly correlated with the regulation of target proteins in treating cancer, such as Akt serine/threonine kinase 1 (Akt1), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), vascular endothelial growth factor A (VEGFA), matrix metallopeptidase-9 (MMP-9), Caspase-3, Fos proto-oncogene, AP-1 transcription factor subunit (FOS), proteoglycans in cancer, estrogen signaling pathway, human immunodeficiency virus 1 infection, hypoxia inducible factor-1 (HIF-1) signaling pathway, tumor necrosis factor(TNF) signaling pathway, microRNAs in cancer and other pathways. Conclusion::The anti-cancer effect of Polygonati Rhizoma-Lilii Bulbus reflects multi-component, multi-target, multi-pathway characteristics of TCM, and provides a scientific basis for explaining the mechanism and material basis of anti-cancer treatment.

Study on Medication Rules of TCM Master LIU Shang-yi for Treatment of Hepatocarcinoma / 中国中医药信息杂志

Objective To explore the medication features of Professor LIU Shang-yi for the treatment of hepatocarcinoma; To provide references for the clinic. Methods Medical cases about hepatocarcinoma treated by Professor LIU Shang-yi in National Medical Center Clinic of Guizhou Provincial TCM Hospital from March 2014 to August 2016 were collected. TCM inheritance support platform software V2.5 was used to analyze properties and flavors, frequency, compatibility law and core medicine combinations. Results Totally 318 prescriptions were included in the study, involving 137 kinds of Chinese materia medica and frequency of 2931 times. The medicines with high frequency were Curcumae Rhizoma, vinegar Trionycis Carapax, Rabdosiae Rubescentis Herba, Ranunculi Ternati Radix and Hypericum Japonicum Thunb; cold and warm were used in the prescriptions, and there were a lot of medicines with flavors of spicy, bitter and sweet. 68 groups of two medicines, 100 groups of three medicines and 72 groups of four medicines with high frequency were obtained by data mining. High frequency association rules were"Curcumae Rhizoma - vinegar Trionycis Carapax", "Curcumae Rhizoma - Rabdosiae Rubescentis Herba", "vinegar Trionycis Carapax - Rabdosiae Rubescentis Herba". Conclusion The prescriptions for the treatment of hepatocarcinoma by Professor LIU Shang-yi have the efficacy of tonifying yin, and resolving masses, clearing heat and detoxifying, which shows the treatment principles of strengthening body resistance and eliminating evil, and adjusting yin and yang.